Lack of integrin α1β1 leads to severe glomerulosclerosis after glomerular injury

Xiwu Chen, Gilbert Moeckel, Jason D. Morrow, Dominic E Cosgrove, Raymond C. Harris, Agnes B. Fogo, Roy Zent, Ambra Pozzi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Severity of fibrosis after injury is determined by the nature of the injury and host genetic susceptibility. Metabolism of collagen, the major component of fibrotic lesions, is in part, regulated by integrins. Using a model of glomerular injury by adriamycin, which induces reactive oxygen species (ROS) production, we demonstrated that integrin α1-null mice develop more severe glomerulosclerosis than wild-type mice. Moreover, primary α1-null mesangial cells produce more ROS both at baseline and after adriamycin treatment. Increased ROS synthesis leads to decreased cell proliferation and increased glomerular collagen IV accumulation that is reversed by antioxidants both in vivo and in vitro. Thus, we have identified integrin α1β1 as a modulator of glomerulosclerosis. In addition, we showed a novel pathway where integrin α1β1 modulates ROS production, which in turn controls collagen turnover and ultimately fibrosis. Because integrin α1β1 is expressed in many cell types this may represent a generalized mechanism of controlling matrix accumulation, which has implications for numerous diseases characterized by fibrosis.

Original languageEnglish (US)
Pages (from-to)617-630
Number of pages14
JournalAmerican Journal of Pathology
Volume165
Issue number2
DOIs
StatePublished - Jan 1 2004

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Integrins
Reactive Oxygen Species
Wounds and Injuries
Fibrosis
Collagen
Doxorubicin
Null Lymphocytes
Mesangial Cells
Genetic Predisposition to Disease
Antioxidants
Cell Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lack of integrin α1β1 leads to severe glomerulosclerosis after glomerular injury. / Chen, Xiwu; Moeckel, Gilbert; Morrow, Jason D.; Cosgrove, Dominic E; Harris, Raymond C.; Fogo, Agnes B.; Zent, Roy; Pozzi, Ambra.

In: American Journal of Pathology, Vol. 165, No. 2, 01.01.2004, p. 617-630.

Research output: Contribution to journalArticle

Chen, X, Moeckel, G, Morrow, JD, Cosgrove, DE, Harris, RC, Fogo, AB, Zent, R & Pozzi, A 2004, 'Lack of integrin α1β1 leads to severe glomerulosclerosis after glomerular injury', American Journal of Pathology, vol. 165, no. 2, pp. 617-630. https://doi.org/10.1016/S0002-9440(10)63326-3
Chen, Xiwu ; Moeckel, Gilbert ; Morrow, Jason D. ; Cosgrove, Dominic E ; Harris, Raymond C. ; Fogo, Agnes B. ; Zent, Roy ; Pozzi, Ambra. / Lack of integrin α1β1 leads to severe glomerulosclerosis after glomerular injury. In: American Journal of Pathology. 2004 ; Vol. 165, No. 2. pp. 617-630.
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