Nephronectin regulates mesangial cell adhesion and behavior in glomeruli

Susan E. Zimmerman, Chitkale Hiremath, Jun Tsunezumi, Zhufeng Yang, Bronwyn Finney, Denise K. Marciano

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 (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.

Original languageEnglish (US)
Pages (from-to)1128-1140
Number of pages13
JournalJournal of the American Society of Nephrology
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Mesangial Cells
Cell Adhesion
Glomerular Basement Membrane
Integrins
Podocytes
Sclerosis
Kidney
Pericytes
Nephrons
nephronectin
In Situ Hybridization
Cell Count
Ligands

ASJC Scopus subject areas

  • Nephrology

Cite this

Nephronectin regulates mesangial cell adhesion and behavior in glomeruli. / Zimmerman, Susan E.; Hiremath, Chitkale; Tsunezumi, Jun; Yang, Zhufeng; Finney, Bronwyn; Marciano, Denise K.

In: Journal of the American Society of Nephrology, Vol. 29, No. 4, 01.04.2018, p. 1128-1140.

Research output: Contribution to journalArticle

Zimmerman, Susan E. ; Hiremath, Chitkale ; Tsunezumi, Jun ; Yang, Zhufeng ; Finney, Bronwyn ; Marciano, Denise K. / Nephronectin regulates mesangial cell adhesion and behavior in glomeruli. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 4. pp. 1128-1140.
@article{15c1a1ce598841c698c293dcc2cf98db,
title = "Nephronectin regulates mesangial cell adhesion and behavior in glomeruli",
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 (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.",
author = "Zimmerman, {Susan E.} and Chitkale Hiremath and Jun Tsunezumi and Zhufeng Yang and Bronwyn Finney and Marciano, {Denise K.}",
year = "2018",
month = "4",
day = "1",
doi = "10.1681/ASN.2017070752",
language = "English (US)",
volume = "29",
pages = "1128--1140",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "4",

}

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.

PY - 2018/4/1

Y1 - 2018/4/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85044760465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044760465&partnerID=8YFLogxK

U2 - 10.1681/ASN.2017070752

DO - 10.1681/ASN.2017070752

M3 - Article

C2 - 29335243

AN - SCOPUS:85044760465

VL - 29

SP - 1128

EP - 1140

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 4

ER -