Vitamin D Ameliorates Podocyte Injury by Enhancing Autophagy Activity in Diabetic Kidney Disease.
Vitamin D Ameliorates Podocyte Injury by Enhancing Autophagy Activity in Diabetic Kidney Disease.
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维生素D通过增强自噬活性改善糖尿病肾病足细胞损伤
DOI：
10.1159/000530403
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发表时间：
2023
影响因子：
2.8
通讯作者：
中科院分区：
文献类型：
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作者：
足细胞自噬的恢复被认为是治疗糖尿病肾病（DKD）的可行策略。本研究旨在探讨维生素D对DKD足细胞损伤的保护作用及其可能机制。2型糖尿病db/db小鼠每天腹腔注射维生素D类似物帕立骨化醇400 ng/kg，持续16周。将永生化的小鼠足细胞培养在含有活性维生素D3骨化三醇或自噬抑制剂3-甲基腺嘌呤的高糖（HG）培养基中。在第24周评估肾功能和尿白蛋白肌酐比值。HE、PAS染色及电镜观察肾组织病理学及形态学变化。免疫组织化学、免疫荧光和Western blot检测肾组织和足细胞中nephrin和podocin的蛋白表达。Western blotting检测自噬相关蛋白（LC 3、Beclin-1、Vps 34）和凋亡相关蛋白（cleaved caspase-3、Bax）的表达。流式细胞仪检测足细胞凋亡。帕立骨化醇给药后，db/db小鼠模型中的白蛋白尿显著减轻。这伴随着减轻系膜基质扩张和足细胞损伤。此外，在帕立骨化醇或骨化三醇治疗后，糖尿病条件下足细胞中受损的自噬也显著增强，伴随着恢复减少的足细胞裂膜蛋白podocin和nephrin。此外，骨化三醇对HG诱导的足细胞凋亡的保护作用可被自噬抑制剂3-甲基腺嘌呤减弱。维生素D通过增强足细胞自噬活性改善DKD足细胞损伤，可能成为DKD治疗干预的潜在候选自噬激活剂。
Restoration of podocyte autophagy is considered as a feasible strategy for the treatment of diabetic kidney disease (DKD). This study aimed at investigating the protective effect and potential mechanism of vitamin D on podocyte injury of DKD. Type 2 diabetic db/db mice received intraperitoneal injections of vitamin D analog paricalcitol 400 ng/kg per day for 16 weeks. Immortalized mouse podocytes were cultured in high glucose (HG) medium with active vitamin D3 calcitriol or autophagy inhibitor 3-methyladenine. Renal function and urine albumin creatinine ratio were assessed at week 24. HE, PAS staining, and electron microscopy were used to evaluate renal histopathology and morphological changes. Immunohistochemistry, immunofluorescence, and Western blot were used to evaluate protein expression of nephrin and podocin in kidney tissue and podocytes. The expression of autophagy-related proteins (LC3, Beclin-1, Vps34) and apoptosis-related proteins (cleaved caspase-3, Bax) was determined by Western blotting. Podocyte apoptosis was further evaluated by using flow cytometer. Albuminuria in a db/db mouse model was markedly attenuated after treatment with paricalcitol. This was accompanied by alleviation of mesangial matrix expansion and podocyte injury. Besides, the impaired autophagy in podocytes under diabetic conditions was also markedly enhanced after paricalcitol or calcitriol treatment, accompanied by restored decreased podocyte slit diaphragm proteins podocin and nephrin. Furthermore, the protective effect of calcitriol against HG-induced podocyte apoptosis could be abated by autophagy inhibitor 3-methyladenine. Vitamin D ameliorates podocyte injury of DKD by enhancing podocyte autophagy activity, which may become a potential candidate autophagy activator for the therapeutic interventions for DKD.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
自噬通过保护高血糖诱导的荚膜细胞损伤，减轻糖尿病肾小球损伤。
影响因子：
3.7
作者：
Fang L;Zhou Y;Cao H;Wen P;Jiang L;He W;Dai C;Yang J
通讯作者：
Yang J
影响因子：
4.2
作者：
Xiao, Houqin;Shi, Wei;Liang, Yongzheng
通讯作者：
Liang, Yongzheng
影响因子：
3
作者：
通讯作者：
--
影响因子：
13.6
作者：
Wang, Youli;Deb, Dilip K.;Li, Yan Chun
通讯作者：
Li, Yan Chun