Tamoxifen inhibits TGF-β/Smad pathway and reduces pathological proliferation of human dermal fibroblasts

Abstract

Objective To explore the function and mechanism of tamoxifen, an estrogen receptor modulator, in the pathogenesis of hyperplatic scar. Methods Primary human fibroblasts were isolated and cultured for 4 generations and then aliquated into 3 groups: control group, TGF-β1 group and TGF-β1+ tamoxifen group. The effects of tamoxifen on human fibrogenic factor production, cell proliferation, migration and differentiation of TGF-β1-induced skin fibroblasts were detected by real-time quantitative polymerase chain reaction (RT-qPCR), MTS, cell scratch test, Western blot and immunofluorescence assay. Results Tamoxifen (10 μmol/L) inhibited the production of collagen 1, collagen 3 and α-SMA induced by TGF-β1 in fibroblasts. MTS results showed that the proliferation activity of TGF-β1 group was higher than that of tamoxifen group (P＜0.05). Wound healing test verified that the migration ability of cells was reduced by tamoxifen intervention. Tamoxifen inhibited collagen secretion and differentiation of skin fibroblasts into muscle fibroblasts. Conclusions The estrogen receptor modulator tamoxifen inhibits pathological proliferation of fibroblasts, so it may be a potential novel strategy for the treatment of hyperplastic scar.

Keywords

• hyperplastic scar| tamoxifen| tgf-β| skin fibroblasts