Objective: The aim of this study was to investigate the effects and mechanism of thalidomide on pancreatic stellate cell (PSC) activation in mice and to find the optimal timing of thalidomide administration.
Methods: PSCs, isolated from mouse pancreas tissue, were divided into five groups with specific treatments: (A) control PSCs (PSC), (B) PSCs induced by TGF-β1 (PSC+TGF-β1), (C) PSCs induced by TGF-β1 followed by thalidomide (PSC+TGF-β1+Thalidomide), (D) PSCs receiving TGF-β1 and thalidomide simultaneously (PSC+(TGF-β1+Thalidomide)), and (E) PSCs treated with thalidomide only (PSC+Thalidomide). We measured the effects of thalidomide on PSC activation by detecting the expression of α-SMA, collagen type I, and the TGF-β/Smad pathway through quantitative real-time PCR and Western blot analysis.
Results: Compared with TGF-β1 alone, thalidomide significantly inhibited PSC activation by reducing α-SMA expression (P<0.05) and decreasing collagen type I deposition (P<0.05). PSCs treated with thalidomide alone showed lower expression of α-SMA and collagen type I than those treated with thalidomide and TGF-β1 at random order (P<0.01). Thalidomide downregulated TGF-β1 and Smad3 and upregulated Smad7 (P<0.05).
Conclusion: Thalidomide could repress PSC activation and alleviate fibrosis by regulating the TGF-β/Smad pathway. Preventive use of thalidomide had maximum effect, and there was no evidence for the reversal of the activation of quiescent PSCs.
Keywords: pancreatic fibrosis; pancreatic stellate cell (PSC); thalidomide; transforming growth factor-β (TGF-β).
© 2021 by the Association of Clinical Scientists, Inc.