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Updated: Nov 16, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

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CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys

Xiaojing Yang1, Wu Luo1, Li Li2

  • 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Toxicology and Applied Pharmacology
|February 25, 2021
PubMed

Insights

Diabetic nephropathy (DN) involves kidney inflammation and fibrosis. Targeting cyclin-dependent kinase 9 (CDK9) with LDC000067 (LDC) reduced these effects and improved kidney function in diabetic mice.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Diabetic nephropathy (DN) is a serious kidney complication of diabetes, characterized by chronic inflammation and fibrosis.
  • Cyclin-dependent kinase 9 (CDK9) has been linked to inflammatory processes and fibrotic development, suggesting a role in DN pathogenesis.

Purpose of the Study:

  • To investigate the role of CDK9 in the development of diabetic nephropathy.
  • To evaluate the therapeutic potential of CDK9 inhibition in a mouse model of DN.

Main Methods:

  • Utilized a streptozotocin-induced type 1 diabetes mouse model and cultured mouse mesangial cells (SV40 MES-13).
  • Administered LDC000067 (LDC), a selective CDK9 inhibitor, to diabetic mice and cultured cells.
  • Assessed inflammatory and fibrogenic markers using mRNA and protein analyses, and measured renal function.

Main Results:

  • LDC treatment significantly reduced inflammatory cytokines and fibrogenic genes in diabetic mouse kidneys, improving renal function.
  • CDK9 inhibition suppressed the activation of the MAPK-AP1 signaling pathway.
  • In cultured cells, CDK9 deficiency or LDC treatment prevented glucose-induced inflammatory and fibrogenic protein expression, also mediated by MAPK-AP1 suppression.

Conclusions:

  • Hyperglycemia activates the CDK9-MAPK-AP1 pathway in the kidney, driving inflammation and fibrosis, ultimately leading to renal dysfunction.
  • CDK9 inhibition represents a promising therapeutic strategy for managing diabetic nephropathy.
Keywords:
Cyclin-dependent kinase 9Diabetic nephropathyHigh glucoseInflammationRenal fibrosis

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