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p38 MAPK pathway is involved in high glucose-induced thioredoxin interacting protein induction in mouse mesangial

Yunzhuo Ren1, Yonghong Shi, Yuehua Wang

  • 1Department of Pathology, Hebei Medical University, and Department of Nephrology, Third Hospital, No. 361 East Zhongshan Road, Shijiazhuang 050017, China.

FEBS Letters
|July 14, 2010
PubMed

Insights

High glucose impairs the thioredoxin (TRX) system

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathophysiology

Background:

  • Diabetic nephropathy involves excessive reactive oxygen species (ROS).
  • The thioredoxin (TRX) system is a key intracellular antioxidant regulator.
  • Understanding ROS regulation in kidney disease is crucial.

Purpose of the Study:

  • Investigate the mechanism by which high glucose affects TRX function in kidney cells.
  • Identify key molecular players in high glucose-induced oxidative stress in diabetic nephropathy.

Main Methods:

  • Utilized mouse mesangial cells (MMCs) cultured under high glucose conditions.
  • Employed gene knockdown techniques to study thioredoxin interacting protein (TXNIP).
  • Assessed TRX activity, p38 MAPK activation, and synthesis of fibronectin and TGF-beta1.

Main Results:

  • High glucose inhibited TRX ROS-scavenging activity in MMCs.
  • This inhibition was mediated by p38 MAPK-induced TXNIP.
  • TXNIP knockdown reversed TRX inhibition and reduced markers of kidney damage.

Conclusions:

  • High glucose-induced TXNIP overexpression, potentially via p38 MAPK, impairs TRX function.
  • Targeting TXNIP may offer a therapeutic strategy for diabetic nephropathy.
  • The p38 MAPK/TXNIP/TRX pathway is critical in high glucose-induced kidney cell damage.

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