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Functional genomics reveals adipose-kidney crosstalk as a contributor to kidney fibrosis via the OSM-OSMR pathway

Jing Zhang1,2, Zhaojun Liu2, Shihui Dong1

  • 1National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.

Functional & Integrative Genomics
|June 1, 2025
PubMed

Insights

Diabetic kidney disease risk is linked to fat tissue function. A specific gene variant in fat tissue increases risk by producing oncostatin-M, which damages kidneys in type 2 diabetes.

Area of Science:

  • Endocrinology
  • Nephrology
  • Genomics

Background:

  • Kidney injury is a serious complication of type 2 diabetes, with varied patient pathophysiology.
  • Abnormal adipose tissue is linked to kidney injury risk, but mechanisms are unclear.

Purpose of the Study:

  • Investigate the relationship between adipose tissue and kidney injury in diabetic nephropathy (DN).
  • Explore the role of adipose functional genomics and genome-wide association studies in understanding DN.

Main Methods:

  • Integrated adipose functional genomics (epigenome, transcriptome, regulatome) with genome-wide association studies of DN.
  • Identified a specific genetic risk variant (rs2412980) and its downstream effects.

Main Results:

  • Constructed a functional genomics map of adipose tissue, highlighting perirenal adipose tissue's role in kidney disease.
  • Discovered that genetic risk for DN is mediated via kidney and adipose-kidney crosstalk.
  • Showed risk variant rs2412980 controls OSM expression in adipose tissue.
  • Demonstrated adipose-derived oncostatin-M (OSM) reprograms renal fibroblasts, activating the OSM-OSMR pathway, linked to reduced eGFR, proteinuria, and creatinine.

Conclusions:

  • Confirmed a genetic link between adipose tissue and kidney disease.
  • Revealed the adipo-renal axis promotes kidney fibrosis in diabetes via the OSM-OSMR pathway.
Keywords:
Diabetic nephropathyFunctional genomicsGenetic riskOSM-OSMR pathwayPerirenal adipose tissueTranscriptional regulation

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