Evidence mapPaperPMID 40103004Full record

ArticleDiabetology & metabolic syndrome2025

Exploring the interplay between adipokine-mediated celastrol target genes and T cells in diabetic nephropathy: a mendelian randomization-based causal inference.

Xiaojuan Wang, Mohamad Hafizi Abu Bakar, Mohd Asyraf Kassim, Khairul Anuar Shariff, Jing Wang, Manli Xu

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Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Xiaojuan WangDepartment of Pharmacy, Taishan Vocational College of Nursing, Tai'an, Shandong, 271099, China.
Mohamad Hafizi Abu BakarBioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia. mhafizi88@usm.my.ORCID http://orcid.org/0000-0001-8064-695X
Mohd Asyraf KassimBioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia.
Khairul Anuar ShariffSchool of Materials & Mineral Resources Engineering, Universiti Sains Malaysia, Nibong Tebal, Penang, 14300, Malaysia.
Jing WangDepartment of Pharmacy, Taishan Vocational College of Nursing, Tai'an, Shandong, 271099, China.
Manli XuDepartment of Pharmacy, Taishan Vocational College of Nursing, Tai'an, Shandong, 271099, China.

Funding

Fundamental Research Grant Scheme, Ministry of Higher Education, Malaysia FRGS/1/2024/STG01/USM/02/1)
6 · The paper itself

Abstract

backgroundDiabetic nephropathy (DN) is influenced by dysregulated adipokines, which play a key role in inflammation, immune responses, and lipid metabolism. However, the precise molecular mechanisms linking adipokine dysregulation, immune cell infiltration, and metabolic reprogramming in DN remain poorly understood. Celastrol, a bioactive lipid regulator, has been shown to mitigate renal immune-inflammatory damage by inhibiting the PI3K/Akt/NF-κB signaling pathway. Yet, its specific impact on adipokine-mediated immune responses and lipid metabolism in DN is unclear. This study aims to elucidate the interplay between adipokine-mediated target genes in DN and investigate how celastrol modulates these interactions.

methodsGene expression profiles of DN patients were obtained from GEO datasets (GSE30122 and GSE30528) and analyzed for differentially expressed genes (DEGs) using the limma package. Gene set variation analysis (GSVA) was conducted to assess lipid metabolism pathways, while Mendelian randomization (MR) and Pearson correlation evaluated the association between DEGs and adipokines. Immune cell infiltration was analyzed using the IOBR R package (MCP-counter and xCell methods), followed by MR analysis of DN-related immune responses. Celastrol target genes were identified using the SEA database.

resultsA total of 70 intersecting DEGs were identified. GSVA revealed that brown and beige adipocyte differentiation pathways were downregulated, while adipocyte-related pathways were upregulated in DN (p < 0.05). MR analysis demonstrated that adiponectin was negatively associated with DN (OR = 0.77, P = 0.005), whereas leptin (OR = 1.92, P = 0.016) and resistin (OR = 1.43, P < 0.001) were positively associated. Three key genes, MAGI2, FGF9, and THBS2 were linked to DN risk and T cell infiltration. THBS2 was positively correlated with T cell infiltration (OR = 0.51, P = 6.7e-06), while FGF9 (OR = -0.8, P = 2.2e-16) and MAGI2 (OR = 0.75, P = 1.3e-13) were negatively correlated. 22 celastrol target genes, including MAGI2, FGF9, and THBS2, were identified.

conclusionOur findings reveal that celastrol modulates DN progression through adipokine-immune crosstalk, with FGF9, MAGI2, and THBS2 emerging as key regulatory genes. These insights provide new avenues for biomarker discovery and therapeutic implications in the development of DN.

Indexed as

AdipokinesCelastrolDiabetic nephropathyImmune cellsImmune infiltrationMendelian randomization

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PMID40103004
PMCPMC11921554

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