Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type
Polarization and Pyroptosis of Macrophages to Improve
Hyperuricemic Nephropathy

Wei      Yin; Jin-Hua      Wang; Yu-Mei      Liang; Kang-Han      Liu; Ying      Chen; Yusa      Chen

doi:10.2174/0115665240272051240122074511

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Abstract

Background: Neferine (Nef) has a renal protective effect. This research intended to explore the impact of Nef on hyperuricemic nephropathy (HN).

Methods: Adenine and potassium oxonate were administered to SD rats to induce the HN model. Bone marrow macrophages (BMDM) and NRK-52E were used to construct a transwell co-culture system. The polarization of BMDM and apoptosis levels were detected using immunofluorescence and flow cytometry. Renal pathological changes were detected using hematoxylin-eosin (HE) and Masson staining. Biochemical methods were adopted to detect serum in rats. CCK-8 and EDU staining were used to assess cell activity and proliferation. RT-qPCR and western blot were adopted to detect NLRC5, NLRP3, pyroptosis, proliferation, and apoptosis-related factor levels.

Results: After Nef treatment, renal injury and fibrosis in HN rats were inhibited, and UA concentration, urinary protein, BUN, and CRE levels were decreased. After Nef intervention, M1 markers, pyroptosis-related factors, and NLRC5 levels in BMDM stimulated with uric acid (UA) treatment were decreased. Meanwhile, the proliferation level of NRK-52E cells co-cultured with UA-treated BMDM was increased, but the apoptosis level was decreased. After NLRC5 overexpression, Nef-induced regulation was reversed, accompanied by increased NLRP3 levels. After NLRP3 was knocked down, the levels of M1-type markers and pyroptosis-related factors were reduced in BMDM.

Conclusion: Nef improved HN by inhibiting macrophages polarized to M1-type and pyroptosis by targeting the NLRC5/NLRP3 pathway. This research provides a scientific theoretical basis for the treatment of HN.

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DOI https://dx.doi.org/10.2174/0115665240272051240122074511	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666

Current Molecular Medicine

Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type Polarization and Pyroptosis of Macrophages to Improve Hyperuricemic Nephropathy

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