Open Access

ARTICLE

Exosomal miR-30a-5p targets NLRP3 to suppress podocyte pyroptosis in diabetic nephropathy

WEI LU^1,*, KAN GUO², DIANMEI XI¹, ZHAOXIA XIA¹

1 Department of Endocrinology and Metabolism, Luzhou People’s Hospital, Luzhou, 646000, China
2 Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, 646000, China

* Corresponding Author: Wei Lu,

(This article belongs to the Special Issue: Cell-Based Regenerative Therapies)

BIOCELL 2023, 47(9), 1995-2008. https://doi.org/10.32604/biocell.2023.024591

Received 07 February 2023; Accepted 26 May 2023; Issue published 28 September 2023

Abstract

Background: Mesenchymal stem cell (MSC)-derived exosomes are closely related to pyroptosis in diabetic nephropathy (DN). This study aimed to explore the protective effect of exosomal miR-30a-5p on podocyte pyroptosis in DN. Methods: Streptozotocin was used to establish the mouse model of DN. Human bone marrow MSC-derived exosomes were extracted and identified via transmission electron microscopy, nanoparticle tracking analysis, and western blotting. MiR-30a-5p mimics and non-control (NC) mimics were transfected into MSCs and podocytes, and exosomes were isolated from the MSCs. High glucose (HG)-induced podocyte model was established to determine the effect of exosomal miR-30a-5p on pyroptosis and inflammation in vitro. Results: MiR-30a-5p was expressed at low levels in DN models, while NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin-N (GSDMD-N), and pro-inflammatory factors (tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-18) were augmented. In vitro, miR-30a-5p expression in the HG-damaged podocytes was down-regulated, while NLRP3 was up-regulated. Interestingly, miR-30a-5p overexpression diminished HG-induced podocyte injury, as proven by increased activity and decreased pyroptosis of podocytes. Concurrently, the up-regulation of miR-30a-5p could inhibit the expression of pro-inflammatory factors, caspase-1, GSDMD-N, and NLRP3 in HG-induced podocytes. MSC-derived exosomal miR- 30a-5p treatment of HG-damaged cells has similar effects to miR-30a-5p mimics treatment. Overexpression of NLRP3 reversed the effect of miR-30a-5p mimics on HG-induced podocytes. Conclusion: This research confirmed that exosomal miR-30a-5p regulates pyroptosis via mediating NLRP3 in DN.

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