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

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

Curr Mol Med. 2024 Feb 16. doi: 10.2174/0115665240272051240122074511. Online ahead of print.

Authors

Wei Yin¹, Jin-Hua Wang¹, Yu-Mei Liang¹, Kang-Han Liu¹, Ying Chen¹, Yusa Chen¹

Affiliation

¹ Department of Nephrology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410002, China.

PMID: 38549521
DOI: 10.2174/0115665240272051240122074511

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.

Keywords: Hyperuricemic nephropathy; Macrophage; NLRC5/NLRP3; Neferine; Pyroptosis.