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

doi:10.1016/j.ydbio.2008.01.022

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^*

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

151 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 β1^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;β1^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 β1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus.

Original language	English (US)
Pages (from-to)	288-301
Number of pages	14
Journal	Developmental Biology
Volume	316
Issue number	2
DOIs	https://doi.org/10.1016/j.ydbio.2008.01.022
State	Published - Apr 15 2008

Funding

We thank Dr. Elaine Fuchs for providing the integrin β1 flox/flox mice. This work was supported by R01-CA94849 (AP); R01-DK74359 (AP); O'Brien Center Grant P50-DK39261-16 (AP, RZ, RCH); P01 DK65123 (DBB, BGH, RZ, AP, JHM), RO1-DK69921 (RZ); R01-DK064687 (JHM), RO1-DK51265 (RCH), Merit award from the Department of Veterans Affairs (RZ, RCH), Established Investigator Award from the American Heart Association (JHM), Grant in Aid American Heart Association (RZ), Research Grant from the National Kidney Foundation of Eastern Missouri and Metro East (GJ).

Keywords

Basement membrane
Development
Kidney
Receptors

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

Access to Document

10.1016/j.ydbio.2008.01.022

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

@article{119fde3f357a44b88a052e1e6f82acf7,

title = "β1 integrin expression by podocytes is required to maintain glomerular structural integrity",

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.",

keywords = "Basement membrane, Development, Kidney, Receptors",

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

note = "Funding Information: We thank Dr. Elaine Fuchs for providing the integrin β1 flox/flox mice. This work was supported by R01-CA94849 (AP); R01-DK74359 (AP); O'Brien Center Grant P50-DK39261-16 (AP, RZ, RCH); P01 DK65123 (DBB, BGH, RZ, AP, JHM), RO1-DK69921 (RZ); R01-DK064687 (JHM), RO1-DK51265 (RCH), Merit award from the Department of Veterans Affairs (RZ, RCH), Established Investigator Award from the American Heart Association (JHM), Grant in Aid American Heart Association (RZ), Research Grant from the National Kidney Foundation of Eastern Missouri and Metro East (GJ).",

year = "2008",

month = apr,

day = "15",

doi = "10.1016/j.ydbio.2008.01.022",

language = "English (US)",

volume = "316",

pages = "288--301",

journal = "Developmental Biology",

issn = "0012-1606",

publisher = "Academic Press Inc.",

number = "2",

}

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 2008, 'β1 integrin expression by podocytes is required to maintain glomerular structural integrity', Developmental Biology, vol. 316, no. 2, pp. 288-301. https://doi.org/10.1016/j.ydbio.2008.01.022

TY - JOUR

T1 - β1 integrin expression by podocytes is required to maintain glomerular structural integrity

AU - Pozzi, Ambra

AU - Jarad, George

AU - Moeckel, Gilbert W.

AU - Coffa, Sergio

AU - Zhang, Xi

AU - Gewin, Leslie

AU - Eremina, Vera

AU - Hudson, Billy G.

AU - Borza, Dorin Bogdan

AU - Harris, Raymond C.

AU - Holzman, Lawrence B.

AU - Phillips, Carrie L.

AU - Fassler, Reinhard

AU - Quaggin, Susan E.

AU - Miner, Jeffrey H.

AU - Zent, Roy

N1 - Funding Information: We thank Dr. Elaine Fuchs for providing the integrin β1 flox/flox mice. This work was supported by R01-CA94849 (AP); R01-DK74359 (AP); O'Brien Center Grant P50-DK39261-16 (AP, RZ, RCH); P01 DK65123 (DBB, BGH, RZ, AP, JHM), RO1-DK69921 (RZ); R01-DK064687 (JHM), RO1-DK51265 (RCH), Merit award from the Department of Veterans Affairs (RZ, RCH), Established Investigator Award from the American Heart Association (JHM), Grant in Aid American Heart Association (RZ), Research Grant from the National Kidney Foundation of Eastern Missouri and Metro East (GJ).

PY - 2008/4/15

Y1 - 2008/4/15

N2 - 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.

AB - 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.

KW - Basement membrane

KW - Development

KW - Kidney

KW - Receptors

UR - http://www.scopus.com/inward/record.url?scp=41149083878&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41149083878&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2008.01.022

DO - 10.1016/j.ydbio.2008.01.022

M3 - Article

C2 - 18328474

AN - SCOPUS:41149083878

SN - 0012-1606

VL - 316

SP - 288

EP - 301

JO - Developmental Biology

JF - Developmental Biology

IS - 2

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this