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"Avaliação da expressão dos receptores de interleucina-8, CXCR1 e CXCR2, e da atividade proliferativa em fibroblastos de quelóide e de pele normal" ; Determination of the interleukin-8 receptors CXCR1 and CXCR2, and proliferative activity in keloids and normal skin fibroblasts

Abdo Filho, Décio
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 05/09/2006 Português
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27.99%
O quelóide é um tumor fibroso benigno que ocorre durante a cicatrização da pele em indivíduos geneticamente predispostos. A cicatrização é um processo biológico complexo e depende da interação de diferentes estruturas teciduais e de um grande número de tipos celulares residentes e infiltrativos, que produzem citocinas. A interleucina 8 (IL-8), citocina pró-inflamatória, é super-expressa pelos fibroblastos durante o desenvolvimento do tecido de granulação, acelerando o processo de cicatrização. Como o quelóide resulta de uma reparação tecidual anormal após lesão da pele, o presente estudo teve por objetivo determinar a expressão dos receptores da IL-8, CXCR1 e CXCR2, e a capacidade proliferativa, pelo ciclo celular, dos fibroblastos queloideanos cultivados e extraídos ex vivo, por citometria de fluxo. Fibroblastos de cicatriz queloideana e de pele normal foram obtidos de 21 pacientes da raça negra, com idade variando entre 10 e 40 anos, de lesões com até 2 anos de evolução. Em nosso estudo constatamos expressão reduzida dos receptores para a IL-8, CXCR1(35,7%±11,2) e CXCR2 (27,8%±11,3), em fibroblastos de cicatriz queloideana cultivados, comparando com a pele normal (44,1±16,2 e 46,3±27,1 respectivamente). Entretanto...

Expressão gênica dos proteoglicanos sindecans-2 e 4 de superfície celular e decorim e versicam de matriz extracelular no quelóide; Gene expression of proteoglycans syndecans-2 and 4 of cell surface and decorin and versican of extracellular matrix in keloid

Boas, Daniel Siquieroli Vilas
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 20/08/2007 Português
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O quelóide é um processo cicatricial, com freqüência aumentada em regiões com maior tensão na pele ou onde a pele é mais espessa, caracterizado por exceder-se além dos limites da lesão que o originou e pela tendência à recidiva após sua ressecção. Ambos os sexos são acometidos, com maior incidência entre a primeira e a terceira década de vida e em indivíduos de etnia negra. A relação familial é sugerida como herança autossômica dominante. O quelóide apresenta características moleculares distintas da pele normal envolvendo uma variedade de sinalizações ainda pouco compreendidas e um aumento da expressão de componentes da matriz extracelular, como o colágeno, os glicosaminoglicanos e os proteoglicanos. Este estudo analisou a expressão gênica dos proteoglicanos de superfície celular sindecam-2 e sindecam-4 e dos de matriz extracelular decorim e versicam no tecido derivado de quelóide de indivíduos não tratados em comparação com a pele clinicamente normal. Participaram desse estudo 10 indivíduos portadores de quelóides (grupo Q) e 10 indivíduos não portadores dessa cicatriz (grupo N). A expressão gênica dos proteoglicanos foi amplificada pela reação em cadeia da polimerase por transcrição reversa e analisada através de eletroforese em gel de agarose. Foi realizada a localização dos proteoglicanos nos tecidos através de reação imunohistoquímica com anticorpos para os sindecans-2 e 4. Os grupos foram comparados pelo teste t de Student. Os proteoglicanos de superfície celular mostraram-se aumentados no grupo Q (93% para o sindecam-2 e 152...

Contração de feridas: revisão bibliográfica e estudo da contração gerada por fibroblastos normais e de quelóides; Wound contraction: literature review and experimental model for the study of the contraction generated by normal and keloid fibroblasts

Kamamoto, Fabio
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 05/01/2007 Português
Relevância na Pesquisa
37.32%
A organização de fibras de colágeno no leito de uma ferida é componente importante da cicatrização e contração da ferida, determinando em última instância a qualidade final da cicatriz. Neste estudo realizamos a implantação de modelo de biotecnologia constituído de géis de colágeno povoados por fibroblastos humanos, que foi utilizado como instrumento para a melhor compreensão dos fenômenos ainda pouco elucidados, envolvidos na contração de feridas. Utilizando fibroblastos procedentes de pele normal ou quelóides, observou-se maior contração dos géis povoados por fibroblastos oriundos de quelóide. O modelo implementado foi considerado eficiente para a avaliação da presença de moduladores da fase de remodelação da cicatriz, tais como o Fator de Crescimento Transformador Beta (TGF beta). A comparação entre a curva de contração gerada por fibroblastos oriudos de pele normal sob o efeito do TGF beta e a contração gerada por fibroblastos de quelóides, demonstra que as mesmas apresentam comportamento igual do ponto de vista estatístico. O modelo proposto demonstrou ser adequado para a melhor compreensão dos mecanismos responsáveis pela contração de feridas, bem como possui potencial na avaliação de novas drogas capazes de modular este fenômeno; An important component of tissue healing and wound contraction is the re-arrangement of ground collagen fibers...

Hamster (Mesocricetus auratus) cheek pouch as an experimental model to investigate human skin and keloid heterologous graft

Hochman,Bernardo; Ferreira,Lydia Masako; Bôas,Flaviane Cássia Vilas; Mariano,Mario
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2004 Português
Relevância na Pesquisa
37.71%
To describe the integration process of grafts of total human skin and keloid in hamster (Mesocricetus auratus) cheek pouch, whose sub-epithelium is naturally an "Immunologically Privileged Site". Fragments of human normal skin and keloid from the breast region of mulatto female patients were transplanted into the cheek pouch subepithelium in situ. Surgical procedure and grafted pouches for microscopic exam at several time points of the transplantation were standardized. The integration of grafted fragments of human skin and keloid was seen in late periods (84 days) since the microscopic assessment showed the presence of blood vases within the conjunctive tissue of grafted fragments. It was also possible to see among the grafted fragments the epithelium, the appearing of early cellular infiltrated, epithelial secretion of keratin, the presence of melanocytes, and delayed changes on the aspect of collagen fibers of conjunctive tissue. Pooled results allow to define hamster cheek pouch sub-epithelium as an experimental model to investigating heterologous graft physiology of human total skin and keloid with epithelium.

Keloid heterograft in the hamster (Mesocricetus auratus) cheek pouch

Hochman,Bernardo; Vilas Bôas,Flaviane Cássia; Mariano,Mario; Ferreira,Lydia Masako
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2005 Português
Relevância na Pesquisa
37.93%
PURPOSE: To study the integration of keloid heterograft in hamster (Mesocricetus auratus) cheek pouch. METHODS: The sample is formed by 18 male hamsters, heterogenic ones, aged between 10 and 14 weeks. Keloid fragments were obtained from keloid scars of the breast region of adult female mulatto patient. Each hamster received keloid fragments into both of its pouches, in a total of 36 grafted fragments. Animals were distributed into 6 groups for having their grafts assessed in the days 5, 12, 21, 42, 84, and 168. A macroscopic assessment is performed by comparing the pouch containing the grafted fragment, at each time point, with the same pouch in the immediate post surgical moment through a comparison of standardized photographs. Under microscope, the presence of blood vases is considered within the conjunctive tissue of the grafted fragment, as a criterion of its integration. Other events, as keratin secretion, the presence of cellular infiltrated, epithelium and keloid collagen fibers aspects are also analyzed. RESULTS: Macroscopy reveals intensive vascularization of the pouch up to 12 days from the transplantation and the presence of constant dark brown pigmentation on the grafted keloid fragments. In microscopy, the integration of keloid fragments is considered by the presence of blood capillary vases within conjunctive tissue. The presence of intensive cellular inflammatory type infiltrated up to 12 days is also observed...

In vitro effect of 470 nm LED (Light Emitting Diode) in keloid fibroblasts

Bonatti,Silvilena; Hochman,Bernardo; Tucci-Viegas,Vanina Monique; Furtado,Fabianne; Pinfildi,Carlos Eduardo; Pedro,Ana Carolina; Ferreira,Lydia Masako
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2011 Português
Relevância na Pesquisa
37.71%
Purpose: To quantify keloid fibroblasts after irradiation with 470nm blue LED, in vitro. Methods: Fibroblasts from keloid and adjacent skin have been obtained from 6 patients. Cells have been cultivated and maintained in DMEM culture medium. In Petri dishes, they were irradiated with energy doses of 6J, 12J and 18J. After 24 h, counting was done by the average of the triplicates for each sample. Results: There were no significant differences in the number of irradiated keloid fibroblasts at the studied doses (p=0.261). In adjacent skin fibroblasts, differences were observed (p=0.025) concerning the doses of 18 J and 6 J (p=0.03). Conclusions: There was a reduction in the number of adjacent skin fibroblasts irradiated with 470nm blue LED at the energy dose of 18 J compared to the ones irradiated at the energy dose of 6 J. There were no changes in keloid fibroblasts counting at any of the doses applied, 24 h after irradiation.

Aggressive keloid-mimicking tumor in Melanosuchus niger in captivity

Pereira,Washington Luiz Assunção; Costa,Antônio Messias; Imbeloni,Aline Amaral; Figueiredo,Thatiana de Andrade; Silva,Klena Sarges Marruaz da
Fonte: Universidade Federal de Santa Maria Publicador: Universidade Federal de Santa Maria
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2013 Português
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The objective of this note is to describe a case of exuberant scarring formation, with keloid characteristics and pseudo-tumoral configuration in a male Black caiman (Melanosuchus niger), with an estimated age of 60 years, belonging to the Zoobotanical Park at the Emílio Goeldi Museum, located in Belém, Pará, Brazil. The alteration appeared on the right posterior limb involving two distal phalanges of the lateral digit and measured 12.4cm at the greatest width. The keloid tissue was surgically removed and samples were processed and analyzed histopathologically, revealing growth made up of fibrous connective tissue with the habitual morphology, which was structurally mature in the more central areas.

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

Russell, S B; Trupin, K M; Rodríguez-Eaton, S; Russell, J D; Trupin, J S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1988 Português
Relevância na Pesquisa
27.9%
Keloids are benign dermal tumors that form during an abnormal wound-healing process in genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloid fibroblasts responded differently than normal adult fibroblasts to transforming growth factor beta. Whereas transforming growth factor beta reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of a growth-control mechanism that is developmentally regulated.

Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing.

Babu, M; Diegelmann, R; Oliver, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1989 Português
Relevância na Pesquisa
27.87%
Wound healing in certain individuals leads to the development of keloid tumors which exhibit abnormal collagen metabolism and an increased abundance of extracellular matrix components. Comparison of fibronectin levels in fibroblasts derived from keloids and normal dermis revealed a relative increase in intracellular and extracellular fibronectin in the keloid-derived cells. While fibronectin was similarly processed, compartmentalized, and degraded by both cell types, fibronectin biosynthesis was found to be accelerated as much as fourfold in keloid fibroblasts due to a corresponding increase in the amount of accumulated fibronectin mRNA. These changes account for the elevated steady-state level of the molecule in keloid fibroblasts and suggest that increased fibronectin in keloid lesions is due to overproduction by the wound-healing fibroblasts. Glucocorticoid treatment stimulated fibronectin biosynthesis in both normal and keloid fibroblasts. However, the amount of stimulation was less for the keloid-derived cells, indicating a limitation on maximal rates of fibronectin biosynthesis. These observations suggest that separate mechanisms act to control basal and maximal rates of fibronectin production. Biosynthesis of the 140-kilodalton fibronectin receptor was also found to be increased in keloid fibroblasts...

Increased Plasminogen Activator Inhibitor-1 in Keloid Fibroblasts May Account for their Elevated Collagen Accumulation in Fibrin Gel Cultures

Tuan, Tai-Lan; Wu, Huayang; Huang, Eunice Y.; Chong, Sheree S. N.; Laug, Walter; Messadi, Diana; Kelly, Paul; Le, Anh
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /05/2003 Português
Relevância na Pesquisa
27.87%
Proteolytic degradation of the provisional fibrin matrix and subsequent substitution by fibroblast-produced collagen are essential features of injury repair. Immunohistochemical studies revealed that although dermal fibroblasts of normal scars and keloids expressed both urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), keloid fibroblasts had a much higher PAI-1 expression. In long-term three-dimensional fibrin gel cultures (the in vitro fibroplasia model), normal fibroblasts expressed moderate and modulated activity levels of uPA and PAI-1. In contrast, keloid fibroblasts expressed a persistently high level of PAI-1 and a low level of uPA. The high PAI-1 activity of keloid fibroblasts correlated with their elevated collagen accumulation in fibrin gel cultures. Substituting collagen for fibrin in the gel matrix resulted in increased uPA activity and reduced collagen accumulation of keloid fibroblasts. Furthermore, decreasing PAI-1 activity of keloid fibroblasts in fibrin gel cultures with anti-PAI-1-neutralizing antibodies also resulted in a reduction in collagen accumulation by keloid fibroblasts. Cumulatively, these results suggest that PAI-1 overexpression is a consistent feature of keloid fibroblasts both in vitro and in vivo...

Heat Shock Proteins Modulate Keloid Formation

Totan, Serhat; Echo, Anthony; Yuksel, Eser
Fonte: Open Science Company, LLC Publicador: Open Science Company, LLC
Tipo: Artigo de Revista Científica
Publicado em 29/04/2011 Português
Relevância na Pesquisa
27.93%
Objective: Heat shock proteins (HSPs) modulate the intensity of the inflammatory and synthetic response to stress in wound healing. Induction of HSPs at the site of wounds improves healing by acting as a molecular chaperone. However, the role of HSPs may augment the inflammatory response, leading to an uncontrolled synthetic process. Propensity for keloid development involves genetic predisposition, physical factors, and an aggressive inflammatory response. The aim of this study is to demonstrate the differential expressions of HSPs in keloid and normal tissues. Methods: Twenty-five keloid and adjacent normal tissue samples were removed from 24 patients who were between 16 and 45 years of age. Western blot, enzyme-linked immunosorbent assay, and immunofluorescence studies were performed to examine hsp27, hsp47, hsp60, hsp70, and hsp90 levels in keloid and normal tissue. Results: Our results demonstrated a significant overexpression of hsp27, hsp47, and hsp70 in keloid tissue compared to that of normal tissue. Statistical analysis using the Student t test revealed a significant difference between these 2 groups (P < .01), while the expression of hsp60 and hsp90 were not significantly different between the keloid and normal tissue samples. Conclusion: The overexpression of HSPs indicates that both a proliferative (hsp70) and a matrix synthesis (hsp47...

Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

Bond, Jennifer E; Bergeron, Andrew; Thurlow, Peter; Selim, M Angelica; Bowers, Edith V; Kuang, Anna; Levinson, Howard
Fonte: ScholarOne Publicador: ScholarOne
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.9%
Aberrant fibroblast migration in response to fibrogenic peptides plays a significant role in keloid pathogenesis. Angiotensin II (Ang II) is an octapeptide hormone recently implicated as a mediator of organ fibrosis and cutaneous repair. Ang II promotes cell migration but its role in keloid fibroblast phenotypic behavior has not been studied. We investigated Ang II signaling in keloid fibroblast behavior as a potential mechanism of disease. Primary human keloid fibroblasts were stimulated to migrate in the presence of Ang II and Ang II receptor 1 (AT1), Ang II receptor 2 (AT2) or nonmuscle myosin II (NMM II) antagonists. Keloid and the surrounding normal dermis were immunostained for NMM IIA, NMM IIB, AT2 and AT1 expression. Primary human keloid fibroblasts were stimulated to migrate with Ang II and the increased migration was inhibited by the AT1 antagonist EMD66684, but not the AT2 antagonist PD123319. Inhibition of the promigratory motor protein NMM II by addition of the specific NMM II antagonist blebbistatin inhibited Ang II–stimulated migration. Ang II stimulation of NMM II protein expression was prevented by AT1 blockade but not by AT2 antagonists. Immunostaining demonstrated increased NMM IIA, NMM IIB and AT1 expression in keloid fibroblasts compared with scant staining in normal surrounding dermis. AT2 immunostaining was absent in keloid and normal human dermal fibroblasts. These results indicate that Ang II mediates keloid fibroblast migration and possibly pathogenesis through AT1 activation and upregulation of NMM II.

Cellular Senescence as a Possible Mechanism for Halting Progression of Keloid Lesions

Varmeh, Shohreh; Egia, Ainara; McGrouther, Duncan; Tahan, Steven R.; Bayat, Ardeshir; Pandolfi, Pier Paolo
Fonte: SAGE Publications Publicador: SAGE Publications
Tipo: Artigo de Revista Científica
Publicado em /11/2011 Português
Relevância na Pesquisa
27.93%
Keloid scarring is a consequence of aberrant wound healing that leads to expansion of the scar beyond the confines of the skin injury. Keloid scars are characterized by excessive extracellular matrix disposition, prolonged proliferation of fibroblasts, increased angiogenesis, and inflammatory cell infiltration. There is no single satisfactory treatment for keloid, and it can lead to severe disfigurements and bodily dysfunction. Thus, clarification of the mechanisms underlying keloid formation, as well as those that prevent it from behaving as a malignant tumor, has significant consequences not only for treatment of keloid but also for the prevention of malignant tumor formation. Senescence is an irreversible form of growth arrest that has been shown to play a role, both in vitro and in vivo, in preventing malignant tumorigenesis upon oncogenic stress. In this study it is shown that fibroblasts embedded inside keloid scars proliferate at a slower rate compared with either those residing at the proliferative edges of the scar or normal fibroblasts. Likewise it is demonstrated that keloid fibroblasts exhibit a cell-cycle arrest with a G2/M DNA content and a higher rate of senescence. The results also indicate that levels of the tumor suppressor protein PML are higher in the active regions of keloid. The study therefore suggests that senescence is one possible mechanism by which keloid is maintained in a benign state. On this basis...

Asiatic Acid Isolated From Centella Asiatica Inhibits TGF-β1-induced Collagen Expression in Human Keloid Fibroblasts via PPAR-γ Activation

Bian, Difei; Zhang, Jizhou; Wu, Xin; Dou, Yannong; Yang, Yan; Tan, Qian; Xia, Yufeng; Gong, Zhunan; Dai, Yue
Fonte: Ivyspring International Publisher Publicador: Ivyspring International Publisher
Tipo: Artigo de Revista Científica
Publicado em 25/10/2013 Português
Relevância na Pesquisa
27.87%
Keloids are fibroproliferative disorders characterized by exuberant extracellular matrix deposition and transforming growth factor (TGF)-β/Smad pathway plays a pivotal role in keloid pathogenesis. Centella asiatica extract has been applied in scar management for ages. As one of its major components, asiatic acid (AA) has been recently reported to inhibit liver fibrosis by blocking TGF-β/Smad pathway. However, its effect on keloid remains unknown. In order to investigate the effects of AA on cell proliferation, invasion and collagen synthesis, normal and keloid fibroblasts were exposed to TGF-β1 with or without AA. Relevant experiments including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay, Transwell invasion assay, enzyme-linked immunosorbent assay, Western blot, quantitative polymerase chain reaction and RNA interference assay were conducted. As a result, keloid fibroblasts showed higher responsiveness to TGF-β1 stimulation than normal fibroblasts in terms of invasion and collagen synthesis. AA could suppress TGF-β1-induced expression of collagen type I, inhibit Smad 2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) expression, while elevate Smad 7 protein level. Noteworthy...

Upregulation of proinflammatory genes in skin lesions may be the cause of keloid formation (Review)

DONG, XIANGLIN; MAO, SHAOLIN; WEN, HAO
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.87%
It was previously demonstrated that the main cause behind keloid formation may be keloid fibroblast abnormalities, which are closely associated with the microenvironment of the keloid lesion. The post-traumatic and chronic inflammation of the keloid lesion area suggest that inflammatory mediators play an important role in the keloid microenvironment and are crucial for keloid fibroblast abnormalities. In this study, we hypothesized that the mechanism underlying keloid formation may involve the continuous upregulation of proinflammatory gene expression in keloid lesions. This hypothesis may explain the inflammatory response, invasive growth and recurrence following resection of keloids, as well as the selective localization of keloids in specific parts of a patient’s body and the differences in localization among different patients.

Mast cell chymase in keloid induces profibrotic response via transforming growth factor-β1/Smad activation in keloid fibroblasts

Dong, Xianglin; Zhang, Chuanshan; Ma, Shaolin; Wen, Hao
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/06/2014 Português
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27.87%
This study was to examine whether mast cell chymase exists in human keloids and exerts its profibrotic effect via transforming growth factor-β1/Smad signaling pathway. The number of mast cells and the expression levels of chymase in keloids and normal skin were examined by immunohistochemistry assays. The mRNA expression and activity changes of chymase in keloids and normal skin were determined by real-time quantitative PCR and radioimmunoassay. After keloid fibroblasts were treated with different concentrations of chymase (0, 15, 30, 60, and 120 ng/mL) for various time periods, the proliferation of keloid fibroblasts, collagen synthesis, mRNA and protein expression of TGF-β1, and the protein expression of phosphorylated Smad2/3, Smad2/3 and Smad7 were investigated using MTT assay, ELISA and Western blotting. Mast cells and chymase exist in keloid. Gene expression and activity of mast cell chymase in keloid are significantly higher than those in normal skin. Chymase promotes keloid fibroblast proliferation and collagen synthesis by activating TGF-β1. The activation of Smad protein signaling pathway by chymase is related to the elevated P-Smad protein expression in keloid fibroblasts. Our data demonstrated that mast cell chymase plays an important role in keloid formation through TGF-β1/Smad signaling pathway.

Non-invasive evaluation of therapeutic response in keloid scar using diffuse reflectance spectroscopy

Hsu, Chao-Kai; Tzeng, Shih-Yu; Yang, Chao-Chun; Lee, Julia Yu-Yun; Huang, Lynn Ling-Huei; Chen, Wan-Rung; Hughes, Michael; Chen, Yu-Wen; Liao, Yu-Kai; Tseng, Sheng-Hao
Fonte: Optical Society of America Publicador: Optical Society of America
Tipo: Artigo de Revista Científica
Publicado em 08/01/2015 Português
Relevância na Pesquisa
27.87%
The pathogenesis and ideal treatment of keloid are still largely unknown, and it is essential to develop an objective assessment of keloid severity to evaluate the therapeutic response. We previously reported that our diffuse reflectance spectroscopy (DRS) system could assist clinicians in understanding the functional and structural condition of keloid scars. The purpose of this study was to understand clinical applicability of our DRS system on evaluating the scar severity and therapeutic response of keloid. We analyzed 228 spectral data from 71 subjects with keloid scars. The scars were classified into mild (0-3), moderate (4-7) and severe (8-11) according to the Vancouver scar scale. We found that as the severity of the scar increased, collagen concentration and water content increased, and the reduced scattering coefficient at 800 nm and oxygen saturation (SaO2) decreased. Using the DRS system, we found that collagen bundles aligned in a specific direction in keloid scars, but not in normal scars. Water content and SaO2 may be utilized as reliable parameters for evaluating the therapeutic response of keloid. In conclusion, the results obtained here suggest that the DRS has potential as an objective technique with which to evaluate keloid scar severity. In addition...

Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro

MA, XIAOYANG; CHEN, JIA; XU, BEI; LONG, XIAO; QIN, HAN; ZHAO, ROBERT CHUNHUA; WANG, XIAOJUN
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.87%
A keloid scar is an overgrowth of dense fibrous tissue that develops around a wound. These scars are raised scars that spread beyong the margins of the orinigal wound to normal skin by invasion. Keloid tissue consists of both an epithelium and dermal fibroblasts. Recent studies have primarily focused on keloid fibroblasts; however, the precise role of keratinocytes in the invasion process of keloids remains to be identified. Hypoxia is a typical characteristic of keloid scars, as well as other solid tumors. The expression of the transcription factor, hypoxia-inducible factor-1α (HIF-1α), is mainly induced by hypoxia and is known for its ability to induce proliferative and transformative changes in cells; its expression has been shown to correlate with tumor invasion and metastasis. In the present study, we used immunohistochemistry, fluorescence staining and western blot analysis and demonstrated that HIF-1α was highly expressed in both the epithelial layer of keloid tissue specimens and in hypoxia-exposed keratinocytes, which suggested that the keloid keratinocytes underwent epithelial-to-mesenchymal transition (EMT) in vitro. The high expression of mesenchymal markers, such as as vimentin and fibronectin was confirmed, as well as the reduced expression of E-cadherin and zonula occludens-1 (ZO-1) during this process by detection at the protein and mRNA level. Moreover...

Hsp70 Knockdown by siRNA Decreased Collagen Production in Keloid Fibroblasts

Shin, Jung U; Lee, Won Jai; Tran, Thanh-Nga; Jung, Inhee; Lee, Ju Hee
Fonte: Yonsei University College of Medicine Publicador: Yonsei University College of Medicine
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.9%
Purpose There are currently no consistently effective treatments for the excessive collagen produced by keloid fibroblasts. Previously, we reported that heat shock protein 70 (Hsp70) is up-regulated in keloid fibroblasts and keloid tissue. We, therefore, investigated whether Hsp70 is related to excessive collagen production in keloid fibroblasts. Materials and Methods We inhibited Hsp70 in keloid fibroblasts by RNA interference and examined the resulting collagen expression. Thus, we selected small interfering RNAs (siRNAs) specific for human Hsp70, transfected them into keloid fibroblasts, and evaluated the resulting phenotypes and protein production using real-time polymerase chain reaction (PCR), Western blot, and a collagen assay. Results: The siRNAs dramatically suppressed Hsp70 mRNA expression, resulting in a decrease in collagen production in the keloid fibroblasts compared with controls. The siRNAs did not influence the viability of the keloid fibroblasts. Conclusion: Hsp70 overexpression likely plays an important role in the excessive collagen production by keloid fibroblasts. RNA interference has therapeutic potential for the treatment of keloids.

O CORPO CUBANO E SEUS PERFORMANCES DO QUELOIDE NA ILHA DO ESPETÁCULO; O CORPO CUBANO E SUAS PERFORMANCES DO QUELÓIDE NA ILHA DO ESPETÁCULO; THE CUBAN BODY AND ITS PERFORMANCES OF THE KELOID IN THE SPECTACLE ISLAND

García Leyva, Luvel; Araújo), (Tradução: Hanna
Fonte: Universidade de São Paulo. Escola de Comunicações e Artes Publicador: Universidade de São Paulo. Escola de Comunicações e Artes
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; Formato: application/pdf
Publicado em 25/06/2014 Português
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O corpo cubano, politizado em seu desempenho, está atravessado pela memória. Uma espécie de encenação atual de eventos políticos que têm suas raízes no passado. Uma performance do "quelóide" que desvela as cicatrizes da cubanidade e nos permite pensar a constituição física de suas complexas relações sociais. Os estudos da performance possibilitam-nos acercar-nos então à corporalidade de cenários sociais cubanos que entretecem uma multiplicidade de diferenças. Nos facilita perceber a mobilidade desse corpo em cenas de adequação, resistência ou subversão frente às lógicas dominantes de fora e de dentro de Cuba.  É nosso potencial de obediência ou revolução.; O corpo cubano, politizado em seu desempenho, está atravessado pela memória. Uma espécie de encenação atual de eventos políticos que têm suas raízes no passado. Uma performance do "quelóide" que desvela as cicatrizes da cubanidade e nos permite pensar a constituição física de suas complexas relações sociais. Os estudos da performance possibilitam trazer-nos então à corporalidade de cenários sociais cubanos que entretecem uma multiplicidade de diferenças. Nos facilita perceber a mobilidade desse corpo em cenas de adequação, resistência ou subversão frente às lógicas dominantes de fora e de dentro de Cuba.  É nosso potencial de obediência ou revolução. ; The Cuban body...