TY - JOUR
T1 - Nephronectin regulates mesangial cell adhesion and behavior in glomeruli
AU - Zimmerman, Susan E.
AU - Hiremath, Chitkale
AU - Tsunezumi, Jun
AU - Yang, Zhufeng
AU - Finney, Bronwyn
AU - Marciano, Denise K.
N1 - Publisher Copyright:
© Copyright 2018 by the American Society of Nephrology.
PY - 2018/4
Y1 - 2018/4
N2 - A critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin (Npnt), a GBM component and known ligand of α8β1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of Npnt from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with α8β1 integrin to novel, specialized adhesion structures that occurred at sites of mesangial cell protrusion at the base of the capillary loops. Absence of nephronectin disrupted these adhesion structures, leading to mislocalization of α8β1. Podocyte-specific deletion of Npnt also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and α8β1 integrin in a newly described adhesion complex and begin to uncover themolecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states.
AB - A critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin (Npnt), a GBM component and known ligand of α8β1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of Npnt from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with α8β1 integrin to novel, specialized adhesion structures that occurred at sites of mesangial cell protrusion at the base of the capillary loops. Absence of nephronectin disrupted these adhesion structures, leading to mislocalization of α8β1. Podocyte-specific deletion of Npnt also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and α8β1 integrin in a newly described adhesion complex and begin to uncover themolecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states.
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U2 - 10.1681/ASN.2017070752
DO - 10.1681/ASN.2017070752
M3 - Article
C2 - 29335243
AN - SCOPUS:85044760465
SN - 1046-6673
VL - 29
SP - 1128
EP - 1140
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 4
ER -