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Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells
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Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells

Published on: March 7, 2025

Glibenclamide prevents increased extracellular matrix formation induced by high glucose concentration in mesangial

Giovanna Giannico1, Pedro Cortes, Mohammed H Baccora

  • 1Div. of Nephrology and Hypertension, Dept. of Medicine, Henry Ford Hospital, Clara Ford Pavilion-5, 2799 West Grand Blvd., Detroit, MI 48202, USA.

American Journal of Physiology. Renal Physiology
|August 10, 2006
PubMed

Insights

Low-dose glibenclamide (Glib) prevents glomerulosclerosis by reducing extracellular matrix accumulation in diabetic kidney cells. This suggests potential therapeutic benefits for type 1 diabetes management.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Sulfonylureas' metabolic effects beyond insulin action are poorly understood.
  • Previous research showed low-dose sulfonylureas prevented glomerulosclerosis in a type 1 diabetes model.
  • High glucose levels in diabetes promote extracellular matrix accumulation in kidney mesangial cells.

Purpose of the Study:

  • To investigate the effects of glibenclamide (Glib) on extracellular matrix deposition in mesangial cells under high glucose conditions.
  • To determine if Glib's effects are dose-dependent and independent of insulin action.

Main Methods:

  • Cultured mesangial cells were exposed to 25 mM glucose for 8 weeks.
  • Cells were treated with varying concentrations of glibenclamide (Glib) during the incubation period.
  • Quantification of collagen I, collagen IV, and fibronectin secretion and deposition, alongside mRNA expression analysis for collagen I and plasminogen inhibitor type-1 (PAI-1).

Main Results:

  • Clinically relevant low concentrations (0.01 microM) of Glib suppressed high glucose-induced accumulation of collagen I, collagen IV, and fibronectin.
  • Glib inhibited collagen I deposition and enhanced collagen I mRNA expression, coupled with suppressed PAI-1 mRNA and protein.
  • These beneficial effects were dose-dependent, with higher Glib concentrations (0.1 or 1 microM) showing absent or reversed effects.

Conclusions:

  • Low-dose glibenclamide (Glib) significantly reduces extracellular matrix accumulation in mesangial cells exposed to high glucose.
  • Glib appears to promote matrix turnover by suppressing PAI-1 transcriptional activity, independent of transforming growth factor-beta1 levels.
  • These findings, along with prior in vivo data, suggest long-term low-dose Glib treatment may prevent glomerulosclerosis in insulin-deficient diabetes.

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