关键词: 泛素-蛋白酶体抑制剂, 肺成纤维细胞, 转化生长因子β1, 活化, 信号转导

Abstract: Objective To investigate the effect of ubiquitin-proteasome inhibitor MG132 on TGF-β1-induced activation in lung fibroblasts and its mechanism. Methods The human embryonic lung fibroblasts (MRC-5) were randomly divided into three groups as follows: control group, TGF-β1 group and MG132 group. The protein levels of a-SMA and COL1A1 were detected by Western blot. The mRNA and protein expression of Smad7, SnoN (Ski-related novel gene N), TβRI, Smad2 and Smad3 were detected by RT-PCR and Western blot respectively. Results TGF-β1 treatment of lung fibroblasts increased α-SMA and COL1A1 expression (P <0.05 as compared with control). MG132 inhibited TGF-β1-induced α-SMA and COL1A1 expression in lung fibroblasts (P <0.05 as compared with TGF-β1 group). The mRNA levels of Smad7 and SnoN in TGF-β1 group were increased (P <0.05 as compared with control). The protein levels of Smad7 and SnoN in TGF-β1 group were decreased (P <0.05 as compared with control). Compared with TGF-β1 group, the protein levels of Smad7 and SnoN in MG132 group were increased (P <0.05). Conclusions MG132 could inhibit TGF-β1-induced activation in lung fibroblasts in vitro, which may be associated with the inhibitory effect of MG132 on TGF-β/Smads signaling by preventing degradation of Smad7 and SnoN.

Key words: Ubiquitin-proteasome inhibitor, lung fibroblast, transforming growth factor-β1, activation, signal transduction