Digestive Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7119-7123. doi: 10.3892/mmr.2017.7445. Epub 2017 Sep 8.
Follistatin‑like 1 (Fstl1) is a secreted glycoprotein that belongs to the follistatin and SPARC (secreted protein, acidic and rich in cysteine) families and was identified to serve a critical role in lung fibrosis. However, the role of Fstl1 in liver fibrosis remains undefined. Therefore, the aim of the present study was to investigate the role of Fstl1 in liver fibrosis. The results indicated that Fstl1 was highly expressed in human hepatic fibrosis tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of Fstl1effectively suppressed HSC proliferation and the protein expression levels of α‑SMA and collagen I in transforming growth factor (TGF)‑β1‑treated HSCs. Mechanistically, knockdown of Fstl1 remarkably decreased the phosphorylation level of Smad3 in TGF‑β1‑induced HSCs. Taken together, the present study demonstrated that Fstl1serves an important role in liver fibrosis and target deletion of Fstl1 attenuated HSCs activation through suppressing TGF‑β1/Smad3 signaling pathway. Therefore, Fstl1 may be a potential therapeutic target for the treatment of liver fibrosis.
卵泡抑素样蛋白 1（Follistatin-like 1，Fstl1）是一种分泌性糖蛋白，属于卵泡抑素和富含半胱氨酸的酸性分泌蛋白（secreted protein，acidic and rich in cysteine，SPARC）家族，其被鉴定在肺纤维化中发挥关键作用。然而，Fstl1 在肝纤维化中的作用尚不清楚。因此，本研究旨在探讨 Fstl1 在肝纤维化中的作用。结果表明，Fstl1 在人肝纤维化组织和活化的肝星状细胞（hepatic stellate cells，HSCs）中高表达。此外，敲低 Fstl1 可有效抑制 TGF-β1 处理的 HSCs 的增殖以及α-平滑肌肌动蛋白和胶原 I 的蛋白表达水平。机制上，敲低 Fstl1 可显著降低 TGF-β1 诱导的 HSCs 中 Smad3 的磷酸化水平。综上所述，本研究表明 Fstl1 在肝纤维化中发挥重要作用，靶向敲除 Fstl1 通过抑制 TGF-β1/Smad3 信号通路可减弱 HSCs 的激活。因此，Fstl1 可能是治疗肝纤维化的潜在治疗靶点。
