Diosgenin protects against podocyte injury in early phase of diabetic nephropathy through regulating SIRT6

尼福林 足细胞 糖尿病肾病 波多辛 医学 肌酐 内科学 薯蓣皂甙元 内分泌学 泌尿科 药理学 化学 糖尿病 蛋白尿 有机化学
作者
Zhi Wang,Qiao Wu,Hongzhan Wang,Yang Gao,Kexin Nie,Yueheng Tang,Hao Su,Meilin Hu,Jing Gong,Ke Fang,Hui Dong
出处
期刊:Phytomedicine [Elsevier BV]
卷期号:104: 154276-154276 被引量:21
标识
DOI:10.1016/j.phymed.2022.154276
摘要

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. DN is the main cause of end-stage renal disease (ESRD). SIRT6 becomes the important target of DN. Diosgenin (a monomer from Chinese herbs) is probable to bind to SIRT6. Based on studies presented in the literature on kidney injuries plus screening for the binding effects of the drug to Sirt6, we aimed to carry out the study to assess the effects of diosgenin involved in improving podocyte damage in the early phase of DN.. DN model was established in spontaneous diabetic db/db mice. Animal experiment was in two parts. The first part includes four groups consisting of control (Con) group, model (Mod) group, low dose of diosgenin (DL) group and high dose of diosgenin (DH) group. The second part includes four groups consisting of control group, model group, DH+OSS_128167 (OSS, inhibitor of SIRT6) group, MDL800 (agonist of SIRT6) group. MPC5 cell line was selected in cell experiment, which was mainly composed of six groups including Con group, palmitic acid (PA) group, PA+DL group, PA+DH group, PA+DH+OSS group, PA+MDL800 group. Some procedures such as transcriptomics, RT-qPCR and so on were used in the study to explore and verify the mechanism. The abnormal changes of mesangial matrix expansion, glomerular basement membrane (GBM) thickness, foot process (FP) width, urine albumin/creatinine (UACR), DESMIN, ADRP, NEPHRIN, PODOCIN, SIRT6 in Mod group were alleviated in DH group rather than DL group in the first part of animal experiment. The effect in DH group could be reversed in DH+OSS group and the same effect was observed in MDL800 group in the second part of animal experiment. The same results were also found in cell experiment. Protein level and mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and Angiopoietin-like-4 (ANGPTL4) were increased in PA group, which could be alleviated in DH group, MDL800 group rather than DH+OSS group. Diosgenin could protect against podocyte injury in early phase of diabetic nephropathy by regulating SIRT6.
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