RESUMO
Dermal papilla cells (DPCs) show phenotypic plasticity during wound healing. The multipotency of DPCs is well recognized, but the signaling pathways that regulate the differentiation of these cells into fibroblasts are poorly understood. A preliminary experiment showed that transforming growth factor beta1 (TGF-ß1) can induce DPCs to differentiate into fibroblast-like cells, which suggests that DPCs may be a source of wound-healing fibroblasts. Bone morphogenetic protein-7 (BMP-7), a member of the TGF-ß superfamily, can prevent and reverse fibrosis by counteracting the TGF-ß1-mediated profibrotic effect. To determine whether BMP-7 attenuates the TGF-ß1-induced differentiation of DPCs into fibroblasts, we established an in vitro system for DPC differentiation and recorded the gene expression patterns that distinguished DPCs from fibroblasts. The proportion of fibroblast-like cells was significantly enhanced in DPCs treated with TGF-ß1, as evidenced by immunocytochemistry, flow cytometry, quantitative real-time reverse transcriptase polymerase chain reaction, and Western blot analysis. BMP-7 and TGF-ß1 administration substantially decreased fibroblast-like differentiation, indicating inhibition of TGF-ß1-induced differentiation. The antagonistic BMP-7- and TGF-ß1-activated signaling pathways can be used to promote wound healing or suppress hypertrophic scarring.
Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Cicatriz Hipertrófica/fisiopatologia , Fibroblastos/metabolismo , Folículo Piloso/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Cicatrização , Actinas/antagonistas & inibidores , Animais , Western Blotting , Proteína Morfogenética Óssea 7/farmacologia , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/prevenção & controle , Feminino , Citometria de Fluxo , Folículo Piloso/citologia , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Vimentina/antagonistas & inibidoresRESUMO
Studies suggest a possible antiscarring effect of basic fibroblast growth factor (bFGF) during wound healing. However, little is known about the precise pathological mechanisms of bFGF. In particular, there is only limited information available about the mechanism of exogenous administration of bFGF to scar formation. To investigate the effect of bFGF on the hypertrophic scar in the rabbit ear model and to clarify the mechanisms of bFGF on treatment for scar in wound healing, the rabbit ear model of wound healing was created and treated topically with bFGF once daily for 3 months; then we examined the changes of macroscopic and histopathological characteristics of scars and the expression of collagen and collagenase-1 (matrix metalloproteinase-1). The results of macroscopic and histologic characteristics revealed a significant difference between scars treated with bFGF and control scars. The expression of collagen in the scars treated with bFGF was decreased, as compared with the scars treated with saline. Further study revealed that bFGF could remarkably enhance expression of matrix metalloproteinase-1. bFGF could improve the quality of wound healing and remarkably alleviate the scar in the rabbit ear model in wound healing, which suggests that bFGF exerted a net negative effecton scar formation in wound healing. The evidence should contribute to a better understanding of the biological activities of bFGF during hypertrophic scar formation.