BAMBI inhibits skin fibrosis in keloid through suppressing TGF-β1-induced hypernomic fibroblast cell proliferation and excessive accumulation of collagen I

摘要

Keloids are scars characterized by pathologically excessive dermal fibrosis and aberrant wound healing. Hypernomic growth of fibroblast cells and excessive accumulation of collagens, especially collagen I, made important contribution to keloid formation. Transforming growth factor-beta 1 (TGF-β1) was a key ruler for the dermal fibrosis. Here, we found that BMP and activin membrane-bound inhibitor (BAMBI), a pseudo-receptor of TGF-β1, was being decreased during the human keloid development and in vitro keloid cell growth. To investigate the effect of BAMBI on keloid development, pcDNA-BAMBI expression vector were transfected into the human primary keloid cells. Then the cell proliferation and viability were detected with EdU and MTT methods and expression of TGF-β1 and collagen I/III were examined by Western blotting analysis. The results showed that, compared to the control, BAMBI overexpression suppressed the cell proliferation and expression of TGF-β1 and collagen I (P < 0.05), whereas, TGFβ1 overexpression rescued the suppression. Finally, pcDNA-BAMBI expression vector was subcutaneously injected into transplanted human keloid in nude mice. During the 6 weeks of in vivo experiment, pcDNA-BAMBI injection significantly suppressed the growth of the implanted keloids and the ratio of collagen I in the keloids. Therefore, BAMBI had an effect on inhibition of keloid growth through suppressing TGF-β1-induced fibroblast cell proliferation and excessive accumulation of collagen I.