Related Experiment Video

Updated: Jun 1, 2025

Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
09:40

Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells

Published on: June 20, 2018

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Deletion of Pyruvate Carboxylase in Tubular Epithelial Cell Promotes Renal Fibrosis by Regulating

Hao Huang1,2,3,4,5, Yuanyuan Han1,3,4,5,6, Yan Zhang1,3,4,5,6

  • 1Department of Nephrology, Xiangya Hospital, Central South University, Changsha, 410008, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 21, 2025
PubMed

Insights

Pyruvate carboxylase (PC) deficiency in kidney cells causes mitochondrial damage and metabolic changes, driving renal fibrosis. This discovery offers new therapeutic targets for chronic kidney disease progression.

Area of Science:

  • Nephrology
  • Mitochondrial Biology
  • Molecular Mechanisms of Disease

Background:

  • Renal fibrosis is a key factor in chronic kidney disease progression.
  • Mitochondrial injury in renal tubular epithelial cells (RTECs) is increasingly recognized as central to renal fibrosis.
  • The precise molecular regulators of this mitochondrial dysfunction remain largely unknown.

Purpose of the Study:

  • To investigate the role of Pyruvate carboxylase (PC) in the pathogenesis of renal fibrosis.
  • To elucidate the molecular mechanisms by which PC deficiency impacts mitochondrial function and metabolism in RTECs.
  • To identify potential therapeutic targets for mitigating renal fibrosis.

Main Methods:

  • Analysis of PC expression in human and animal fibrotic kidney samples.
  • Generation and study of renal proximal tubule-specific Pcx gene knockout mice (PcxcKO).
  • Utilized a stable PC knock-out renal tubular epithelial cell (RTEC) line for mechanistic studies.

Main Results:

  • Downregulation of PC was observed in fibrotic kidney tissues.
  • PcxcKO mice exhibited significant interstitial fibrosis and increased extracellular matrix deposition.
  • PC deficiency disrupted the PC-SQOR interaction, leading to SQOR degradation, mitochondrial dysfunction, mtDNA release, cGAS-STING activation, and increased glycolysis.

Conclusions:

  • PC deficiency is a critical driver of mitochondrial injury and metabolic reprogramming in RTECs, promoting renal fibrosis.
  • The findings reveal a novel mechanism linking PC, mitochondrial integrity, and the cGAS-STING pathway in kidney fibrosis.
  • PC emerges as a potential therapeutic target for treating renal fibrosis and chronic kidney disease.
Keywords:
SQORcGAS‐STINGglycolysispyruvate carboxylaserenal fibrosis

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