Department of Nephrology, Postdoctoral Workstation of Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, 030012, China; Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Mol Cell Endocrinol. 2021 May 15;528:111224. doi: 10.1016/j.mce.2021.111224. Epub 2021 Mar 4.
Intermedin(IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family that has anti-inflammatory, antioxidant and anti-apoptosis properties. This study aimed to evaluate the renoprotective effects of IMD on podocyte apoptotic loss and slit diaphragm protein deficiency the kidneys of rats with in streptozotocin (STZ) induced diabetes in high glucose-exposed podocytes. Our results showed that IMD significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure in vivo. IMD also improved the induction of slit diaphragm proteins, and restored the decreased Bcl-2 expression and suppressed Bax and caspase-3 induction in the diabetic glomeruli. In addition, IMD attenuated podocyte apoptosis and filamentous actin (F-actin) rearrangement in high glucose-exposed podocytes. Exposure to high glucose elevated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress in renal podocytes, and IMD treatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vivo and in vitro. These observations demonstrate that targeting ER stress is an underlying mechanism of IMD-mediated amelioration of diabetes-associated podocyte injury and dysfunction.
中介素（IMD）是降钙素/降钙素基因相关肽（CT/CGRP）家族的一个新成员，具有抗炎、抗氧化和抗细胞凋亡的特性。本研究旨在评估 IMD 在高糖暴露的足细胞中对链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏足细胞凋亡和裂孔隔膜蛋白缺失的肾保护作用。我们的结果表明，IMD 可显著减轻蛋白尿，并缓解体内肾小球超微结构的异常改变。IMD 还改善了裂孔隔膜蛋白的诱导，并恢复了糖尿病肾小球中下调的 Bcl-2 表达和抑制 Bax 和 caspase-3 的诱导。此外，IMD 可减轻高糖暴露的足细胞中的凋亡和丝状肌动蛋白（F-actin）重排。高糖暴露会增加内质网（ER）应激在肾脏足细胞中的未折叠蛋白反应（UPR），而 IMD 处理可阻断与足细胞凋亡和减少裂孔隔膜蛋白合成相关的 ER 应激反应，无论是在体内还是体外。这些观察结果表明，靶向 ER 应激是 IMD 介导改善糖尿病相关足细胞损伤和功能障碍的潜在机制。
