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. 2025 Feb;57(2):643-653.
doi: 10.1007/s11255-024-04214-2. Epub 2024 Oct 9.

NSUN2 knockdown inhibits macrophage infiltration in diabetic nephropathy via reducing N5-methylcytosine methylation of SOCS1

Ru Wang #  1 , Jianchang Qu #  2 , Meiqiong Chen #  3 , Tenglong Han  1 , Zhipeng Liu  4 , Huizhong Wang  5
Affiliations

NSUN2 knockdown inhibits macrophage infiltration in diabetic nephropathy via reducing N5-methylcytosine methylation of SOCS1

Ru Wang et al. Int Urol Nephrol. 2025 Feb.

Abstract

Objective: N5-methylcytosine (m5C) methylation is involved in various disease progression; however, its role in diabetic nephropathy (DN) has not been studied. The aim of this study was to investigate the role of NSUN2 in DN and the underlying mechanism.

Methods: Streptozotocin-induced experimental mouse model was generated to analyze the role of NSUN2 in vivo, and high glucose (HG)-treated Raw264.7 cells were used to assess the effect of NSUN2 on macrophage infiltration in vitro. The regulation of NSUN2 on SOCS1 m5C methylation was evaluated using m5C methylated RNA immunoprecipitation, luciferase reporter analysis, and RNA stability determination assay.

Results: The results indicated that NSUN2 was highly expressed in the blood and kidney of DN mice. Knockdown of NSUN2 alleviated kidney damage, reduced blood glucose and urine albumin, and suppressed macrophage infiltration in DN mice. Moreover, NSUN2 interacted with SOCS1, and silenced NSUN2 inhibited m5C levels of SOCS1 to reduce SOCS1 mRNA stability. Additionally, interference with NSUN2 suppressed macrophage migration, invasion, and infiltration by positively regulating SOCS1 expression under HG conditions.

Conclusion: In conclusion, silencing of NSUN2 inhibits macrophage infiltration by reducing m5C modification of SOCS1, and thereby attenuates renal injury. The findings suggest a novel regulatory mechanism between NSUN2-mediated m5C modification and DN.

Keywords: Diabetic nephropathy; M5C methylation; Macrophage infiltration; NSUN2; SOCS1.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The study was approved by the Ethics Committee of The 305 Hospital of PLA. All experiments were performed in accordance with relevant guidelines and regulations.

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