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

Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta 1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta 1 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 beta 1 integrin in the podocyte by crossing beta 1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary fort-nation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;beta 1(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 p I containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus. (C) 2008 Elsevier Inc. All rights reserved.