β1 integrin expression by podocytes is required to maintain glomerular structural integrity

Ambra Pozzi, George Jarad, Gilbert W. Moeckel, Sergio Coffa, Xi Zhang, Leslie Gewin, Vera Eremina, Billy G. Hudson, Dorin Bogdan Borza, Raymond C. Harris, Lawrence B. Holzman, Carrie L. Phillips, Reinhard Fassler, Susan E. Quaggin, Jeffrey H. Miner, Roy Zent

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). β1, the most abundantly expressed integrin subunit, binds at least 12 α subunits. β1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted β1 integrin in the podocyte by crossing β1flox/flox mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;β1flox/flox mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of β1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus.

Original languageEnglish (US)
Pages (from-to)288-301
Number of pages14
JournalDevelopmental Biology
Volume316
Issue number2
DOIs
StatePublished - Apr 15 2008

Keywords

  • Basement membrane
  • Development
  • Kidney
  • Receptors

ASJC Scopus subject areas

  • Developmental Biology

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  • Cite this

    Pozzi, A., Jarad, G., Moeckel, G. W., Coffa, S., Zhang, X., Gewin, L., Eremina, V., Hudson, B. G., Borza, D. B., Harris, R. C., Holzman, L. B., Phillips, C. L., Fassler, R., Quaggin, S. E., Miner, J. H., & Zent, R. (2008). β1 integrin expression by podocytes is required to maintain glomerular structural integrity. Developmental Biology, 316(2), 288-301. https://doi.org/10.1016/j.ydbio.2008.01.022