Integrin α1β1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation

Xiwu Chen, Tristin D. Abair, Maria R. Ibanez, Yan Su, Mark R. Frey, Rebecca S. Dise, D. Brent Polk, Amar B. Singh, Raymond C. Harris, Roy Zent, Ambra Pozzi

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin α1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by α1-null mesangial cells. In the present studies, we describe the mechanism whereby integral α1-null mesangial cells produce excessive ROS. Integrili α1-null mesangial cells have constitatively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in α1-null mesangial cells. Thus, our study demonstrates that integrin α1β1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.

Original languageEnglish (US)
Pages (from-to)3313-3326
Number of pages14
JournalMolecular and cellular biology
Volume27
Issue number9
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Chen, X., Abair, T. D., Ibanez, M. R., Su, Y., Frey, M. R., Dise, R. S., Polk, D. B., Singh, A. B., Harris, R. C., Zent, R., & Pozzi, A. (2007). Integrin α1β1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation. Molecular and cellular biology, 27(9), 3313-3326. https://doi.org/10.1128/MCB.01476-06