Department of Geriatrics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Geriatrics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Cell Physiol. 2018 Nov;233(11):9007-9014. doi: 10.1002/jcp.26846. Epub 2018 Jun 1.
Endothelial-mesenchymal transition (EndMT) plays a pivotal role in organ fibrosis. This study examined the effect of SIRT1 on transforming growth factor beta (TGF-β)-induced EndMT in human endothelial cells (ECs) and its probable molecular mechanism. We assessed EndMT by immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and migration and invasion assays. Adenovirus was used to overexpress or knockdown SIRT1 in ECs. The regulatory relationship between SIRT1 and Smad4 was analyzed by coimmunoprecipitation assay. We found that SIRT1 was decreased in TGF-β-induced EndMT, and SIRT1 inhibited TGF-β-induced EndMT through deacetylating Smad4. Our findings suggest that SIRT1 has an important role in inhibiting EndMT by regulating the TGF-β/Smad4 pathway in human ECs and, thus, protecting against fibrosis.
内皮-间充质转化（EndMT）在器官纤维化中起着关键作用。本研究探讨了 SIRT1 对人内皮细胞（ECs）中转化生长因子-β（TGF-β）诱导的 EndMT 的影响及其可能的分子机制。我们通过免疫荧光染色、实时定量聚合酶链反应、Western blot 和迁移及侵袭实验评估 EndMT。腺病毒用于过表达或敲低 ECs 中的 SIRT1。通过共免疫沉淀实验分析 SIRT1 和 Smad4 之间的调节关系。我们发现，SIRT1 在 TGF-β诱导的 EndMT 中减少，SIRT1 通过去乙酰化 Smad4 抑制 TGF-β诱导的 EndMT。我们的研究结果表明，SIRT1 通过调节人 ECs 中的 TGF-β/Smad4 通路在抑制 EndMT 中起重要作用，从而防止纤维化。
