Mechanical stretch-induced fibronectin and transforming growth factor- β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent

Gabriella Gruden, Silvia Zonca, Anthea Hayward, Stephen Thomas, Sabrina Maestrini, Luigi Gnudi, GianCarlo Viberti

Research output: Contribution to journalArticlepeer-review

Abstract

Hemodynamic abnormalities are important in the pathogenesis of the excess mesangial matrix deposition of diabetic and other glomerulopathies. p38-Mitogen-activated protein (MAP) kinase, an important intracellular signaling molecule, is activated in the glomeruli of diabetic rats. We studied, in human mesangial cells, the effect of stretch on p38 MAP kinase activation and the role of p38 MAP kinase in stretch-induced fibronectin and transforming growth factor-β1 (TGF-β1) accumulation, p38 MAP kinase was activated by stretch in a rapid (11-fold increase at 30 min, P <0.001) and sustained manner (3-fold increase at 33 h, P <0.001); this activation was mediated by protein kinase C (PKC). Stretch-induced fibronectin and TGF-β1 protein levels were completely abolished (100% inhibition, P <0.001; and 92% inhibition, P <0.01, respectively) by SB203580, a specific p38 MAP kinase inhibitor. At 33 h, TGF-β1 blockade did not affect stretch-induced fibronectin production, but partially prevented stretch-induced p38 MAP kinase activation (59% inhibition, P <0.05). TGF-β1 induced fibronectin accumulation after 72 h of exposure via a p38 MAP kinase-dependent mechanism (30% increase over control, P <0.01). In human mesangial cells, stretch activates, via a PKC-dependent mechanism, p38 MAP kinase, which independently induces TGF-β1 and fibronectin. In turn, TGF-β1 contributes to maintaining late p38 MAP kinase activation, which perpetuates fibronectin accumulation.

Original languageEnglish
Pages (from-to)655-661
Number of pages7
JournalDiabetes
Volume49
Issue number4
Publication statusPublished - Apr 2000

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Mechanical stretch-induced fibronectin and transforming growth factor- β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent'. Together they form a unique fingerprint.

Cite this