Leslie Gewin
Faculty Member
Last active: 3/26/2019

Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.

Pozzi A, Jarad G, Moeckel GW, Coffa S, Zhang X, Gewin L, Eremina V, Hudson BG, Borza DB, Harris RC, Holzman LB, Phillips CL, Fassler R, Quaggin SE, Miner JH, Zent R
Dev Biol. 2008 316 (2): 288-301

PMID: 18328474 · PMCID: PMC2396524 · DOI:10.1016/j.ydbio.2008.01.022

Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta1 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 beta1 integrin in the podocyte by crossing beta1(flox/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;beta1(flox/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 beta1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus.

MeSH Terms (14)

Aging Animals Animals, Newborn DNA Primers Gene Expression Regulation In Situ Hybridization Integrin beta1 Kidney Glomerulus Mice Mice, Knockout Mice, Transgenic Podocytes Polymerase Chain Reaction Proteinuria

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