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Activation of mTOR mediates hyperglycemia-induced renal glomerular endothelial hyperpermeability via the

Xiaolin Chen1,2, Jianhui Chen3, Xianfan Li3

  • 1Department of Clinical Laboratory, Pingxiang People's Hospital, Pingxiang, 337000, Jiangxi, China. cxl888hhh@163.com.

Diabetology & Metabolic Syndrome
|October 10, 2021
PubMed
Abstract

Insights

High glucose damages the kidney

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Diabetic nephropathy is characterized by albuminuria and glomerular endothelial dysfunction.
  • The mechanistic target of rapamycin (mTOR) and RhoA/ROCK pathways regulate the glomerular filtration barrier (GFB).
  • The role of these pathways in high glucose-induced GFB dysfunction in human renal glomerular endothelial cells (HRGECs) is unclear.

Purpose of the Study:

  • To investigate the mechanisms of high glucose-induced GFB dysfunction in HRGECs.
  • To elucidate the involvement of mTOR and RhoA/ROCK signaling pathways in this process.

Main Methods:

  • HRGECs were exposed to high glucose (HG) with or without rapamycin.
  • Albumin leakage and transendothelial electrical resistance were measured.
  • F-actin reorganization, myosin light chain (MLC) phosphorylation, and RhoA activity were assessed.

Main Results:

  • HG induced F-actin reorganization and MLC phosphorylation, disrupting the endothelial barrier.
  • Rapamycin and RhoA/ROCK inhibition attenuated HG-induced barrier disruption.
  • HG upregulated RhoA activity via an mTOR-dependent pathway, leading to MLC phosphorylation and cytoskeleton rearrangement.

Conclusions:

  • High glucose induces glomerular endothelial barrier dysfunction through an mTOR-dependent upregulation of RhoA/ROCK signaling.
  • This pathway mediates MLC phosphorylation and endothelial cell cytoskeleton rearrangement.
  • Targeting mTOR or RhoA/ROCK may offer therapeutic strategies for diabetic nephropathy.
Keywords:
Glomerular endothelial cellHigh glucoseMyosin light chainPermeabilityRhoA/ROCK

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