• Biomed. Pharmacother. · Dec 2018

    Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression.

    • Xiaoping Chen, Lei Zhao, Yanwei Xing, and Bo Lin.
    • Department of Endocrinology, The First Affiliated Hospital of Henan University, Kaifeng, 475000, China.
    • Biomed. Pharmacother. 2018 Dec 1; 108: 7-14.

    BackgroundSeveral miRNAs including miR-21 have emerged as important regulators in the development of diabetic nephropathy (DN). However, the molecular mechanism of miR-21 underlying DN pathogenesis remains to be further discussed.MethodsStreptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes were used as the in vivo and in vitro models of DN. miR-21 level was detected by qRT-PCR assay. Inflammatory cytokine levels were assessed by ELISA. Kidney injury of rats was evaluated by blood glucose, serum creatinine and blood urine nitrogen concentrations and periodic acid schiff (PAS) staining. Apoptosis in kidney tissues and podocytes was determined by TUNEL and flow cytometry analyses, respectively. Western blot analysis was applied to measure the protein levels of tissue inhibitors of metalloproteinase 3 (TIMP3), Bax and Bcl-2. The relationship between TIMP3 and miR-21 was confirmed by luciferase reporter assay.ResultsmiR-21 expression was upregulated in serum and kidney tissues of DN patients, kidney tissues of STZ-induced DN rats, and HG-treated podocytes. miR-21 depletion inhibited pro-inflammatory factor (IL-1β, TNF-α) secretions and alleviated kidney damages in STZ-induced DN rats. Moreover, TIMP3 was a target of miR-21 in HG-treated podocytes. Additionally, TIMP3 overexpression abated HG-induced inflammatory responses and podocyte apoptosis. Furthermore, the inhibitory effects of TIMP3 on inflammatory responses and podocyte apoptosis were alleviated by increased miR-21.ConclusionThe down-regulation of miR-21 inhibited the progression of DN by targeting TIMP3 in STZ-induced DN rats and HG-treated podocytes, elucidating a novel regulatory mechanism of miR-21 in DN progression and offering a potential target for DN therapy.Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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