Heat shock protein 22 reduces the activation of cardiac fibroblasts induced by transforming growth factor β1 / 中华急诊医学杂志

ABSTRACT

Objective:To explore the effect of Hsp22 on the activation of cardiac fibroblasts stimulated by TGFβ1 and its possible molecular mechanism.Methods:Cardiac fibroblasts of adult mice were isolated and cultured, and stimulated with TGFβ1 to induce fibroblast activation. Fibroblasts were incubated with Hsp22 of different concentrations (1, 2, 4, 8, 10 μg/mL) for 24 h, and their activation, proliferation and secretion were observed. CCK8 kit was used to detect cell proliferation. RT-PCR was used to detect the transcription of fibrogenic factor. Immunofluorescence was used to detect the expression of α-SMA protein. Immunoblotting was used to detect the possible signal protein.Results:CCK8 results showed that fibroblast increased significantly after TGFβ1 stimulation ( P<0.05). The expression of α-SMA in fibroblasts and the transcription of fibrosis-related genes increased significantly after TGFβ1 stimulation ( P<0.05). Different concentrations (1, 2, 4, 8, and 10 μg/mL) of Hsp22 all inhibited the proliferation of fibroblasts significantly (( P<0.05). Eight μg/mL and 10 μg/mL Hsp22 inhibited the expression of α-SMA ( P<0.05). and reduced the transcription of fibrosis-related genes ( P<0.05). Immunoblotting results indicated that after induced by TGFβ1, the expression of WNT and β-catenin, the phosphorylation level of GSK3β, and the nuclear translocation of β-catenin increased ( P<0.05). Ten μg/mL Hsp22 inhibited the expression of WNT and β-catenin, and reduced the phosphorylation of GSK3β the nuclear translocation of β-catenin and the phosphorylation of smad2 and smad3( P<0.05). Conclusions:Hsp22 could block TGFβ1-induced fibroblast activation, proliferation and secretion via inhibiting the WNT/β-catenin signaling pathway.