Title | Nephronectin Regulates Mesangial Cell Adhesion and Behavior in Glomeruli. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Zimmerman SE, Hiremath C, Tsunezumi J, Yang Z, Finney B, Marciano DK |
Journal | J Am Soc Nephrol |
Volume | 29 |
Issue | 4 |
Pagination | 1128-1140 |
Date Published | 2018 Apr |
ISSN | 1533-3450 |
Abstract | 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 (), a GBM component and known ligand of 81 integrin. Immunolocalization and hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with 81 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 81. Podocyte-specific deletion of also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and 81 integrin in a newly described adhesion complex and begin to uncover the molecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states. |
DOI | 10.1681/ASN.2017070752 |
Alternate Journal | J. Am. Soc. Nephrol. |
PubMed ID | 29335243 |
PubMed Central ID | PMC5875951 |
Grant List | P30 DK079328 / DK / NIDDK NIH HHS / United States R01 DK099478 / DK / NIDDK NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:13pm