Evidence mapPaperPMID 41527491Full record

ArticleEndocrinology, diabetes & metabolism2026

Diabetic Kidney Disease Progression Alleviated in Mice by ALKBH5-Mediated UC-MSCs-Derived Exosomes That Inhibit TRAF6 m6A Modification and Promote M2 Macrophage Polarisation.

Lei Li, Hongmei Liu, Huanhuan Wang, Yu Mao, Lige Song, Zhiqiang Kang

Abstract read
In one paragraph

Article in Endocrinology, diabetes & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Lei LiDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.
Hongmei LiuDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.
Huanhuan WangDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.
Yu MaoDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.
Lige SongDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.
Zhiqiang KangDepartment of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan Province, China.

Funding

Medical Research Project of Zhengzhou City in 2024 ZZYK2024033
6 · The paper itself

Abstract

backgroundDiabetic kidney disease (DKD) is a major diabetes complication with limited treatment options. Exosomes (Exo) from umbilical cord mesenchymal stem cells (UC-MSCs) have shown therapeutic promise. The role of alkylation repair homologue protein 5 (ALKBH5)-modified UC-MSCs Exo in regulating macrophage polarisation and alleviating DKD is investigated.

methodsDKD-associated inflammation was modelled by Lipopolysaccharide (LPS)/interferon-gamma (IFN-γ)-stimulated RAW264.7 macrophages. RT-qPCR and western blotting were employed to analyse mRNA and protein expression. Exosomes from ALKBH5-modified UC-MSCs were isolated and characterised. Macrophage polarisation (M1/M2) was assessed by flow cytometry, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). Tumor necrosis factor receptor-associated factor 6 (TRAF6) N6-methyladenosine (m6A) modification and expression were analysed via methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) assays. The DKD model was established using spontaneous diabetic db/db mice. The renal function of mice was evaluated by ELISA and commercial assay kits. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson's trichrome staining were performed to assess the renal histopathology of mice.

resultsALKBH5 overexpression promoted M2 and inhibited M1 macrophage polarisation. ALKBH5 downregulated TRAF6 via m6A demethylation. ALKBH5-modified UC-MSCs Exo enhanced M2 polarisation and suppressed M1 phenotype in vitro. In DKD mice, ALKBH5-modified UC-MSCs Exo mitigated renal injury. Moreover, these exosomes enhanced anti-inflammatory responses and promoted M2 macrophage polarisation in DKD mice.

conclusionALKBH5-modified UC-MSCs Exo reduced TRAF6 expression by demethylating its m6A sites, promoting M2 macrophage polarisation and alleviating DKD progression. These findings suggested that ALKBH5-modified UC-MSCs Exo might represent a promising therapeutic approach for DKD.

Indexed as

AlkB Homolog 5, RNA DemethylaseDiabetic NephropathiesExosomesMacrophagesMesenchymal Stem CellsTNF Receptor-Associated Factor 6AdenosineAnimalsDisease ProgressionHumansMacrophage ActivationMaleMiceMice, Inbred C57BLRAW 264.7 CellsRNA MethylationAdenosineALKBH5 protein, humanALKBH5 protein, mouseAlkB Homolog 5, RNA DemethylaseTNF Receptor-Associated Factor 6TRAF6 protein, mouseALKBH5diabetic kidney diseaseexosomesTRAF6umbilical cord mesenchymal stem cells

Identifiers

PMID41527491
PMCPMC12796834

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.