Beta1 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). 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.
Pozzi
Ambra
A
Department of Medicine, Veterans Affairs Hospital, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jarad
George
G
Moeckel
Gilbert W
GW
Coffa
Sergio
S
Zhang
Xi
X
Gewin
Leslie
L
Eremina
Vera
V
Hudson
Billy G
BG
Borza
Dorin-Bogdan
DB
Harris
Raymond C
RC
Holzman
Lawrence B
LB
Phillips
Carrie L
CL
Fassler
Reinhard
R
Quaggin
Susan E
SE
Miner
Jeffrey H
JH
Zent
Roy
R
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D017931:DNA Primers; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000235:genetics*; D007678:Kidney Glomerulus / Q000033:anatomy & histology / Q000254:growth & development* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050199:Podocytes / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011507:Proteinuria / Q000235:genetics
D017931:DNA Primers; D019012:Integrin beta1