Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, PR China.
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, PR China.
Cell Signal. 2021 Jul;83:109983. doi: 10.1016/j.cellsig.2021.109983. Epub 2021 Mar 17.
Autophagy is a lysosomal degradative process that is closely related to the pathogenesis of vascular calcification. Recent evidence suggests that periostin (POSTN) is a unique extracellular matrix protein that is associated with diabetic vascular complications. The aim of current study is to investigate the role of POSTN in diabetic vascular calcification and the underlying mechanisms. Results showed that POSTN was highly upregulated in both calcified arteries of diabetic rats and AGEs-BSA mediated vascular smooth muscle cell (VSMC) calcification. POSTN blocked autophagic flux during the diabetic calcification process, as evidenced by increased protein expression of Beclin1, LC3-II, and P62, as well as the co-localization of LC3-II and LAMP1. Inhibition of POSTN alleviated AGEs-BSA-induced autophagic flux blockade, thereby attenuating AGEs-BSA-induced VSMC calcification. Mechanistically, the upregulation of POSTN impaired the fusion of autophagosomes and lysosome and resulted in the autophagic flux blockade in AGEs-BSA-treated VSMC. Furthermore, this autophagic blockade was intracellular ROS-dependent. In summary, this study uncovered a novel mechanism of POSTN in autophagy regulation of diabetic vascular calcification.
自噬是一种溶酶体降解过程，与血管钙化的发病机制密切相关。最近的证据表明，骨桥蛋白（POSTN）是一种独特的细胞外基质蛋白，与糖尿病血管并发症有关。本研究旨在探讨 POSTN 在糖尿病血管钙化中的作用及其潜在机制。结果表明，糖尿病大鼠钙化动脉和 AGEs-BSA 介导的血管平滑肌细胞（VSMC）钙化中 POSTN 均高度上调。POSTN 在糖尿病钙化过程中阻断自噬流，这表现在 Beclin1、LC3-II 和 P62 的蛋白表达增加，以及 LC3-II 和 LAMP1 的共定位。抑制 POSTN 减轻了 AGEs-BSA 诱导的自噬流阻断，从而减轻了 AGEs-BSA 诱导的 VSMC 钙化。在机制上，POSTN 的上调损害了自噬体和溶酶体的融合，导致 AGEs-BSA 处理的 VSMC 中的自噬流阻断。此外，这种自噬阻断是细胞内 ROS 依赖性的。总之，本研究揭示了 POSTN 在糖尿病血管钙化中自噬调节的新机制。
