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Lack of N‐Sulfation of Podocyte Cell Surface Heparan Sulfate Glycosaminoglycans Leads to Abnormalities in Podocyte Organization, Adhesion, and Migration
Author(s) -
Sugar Terrel A,
McCarthy Deborah J.,
Esko Jeffrey D.,
Holzman Lawrence B.,
McCarthy Kevin J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.906.1
Subject(s) - perlecan , podocyte , sulfation , glycosaminoglycan , heparan sulfate , microbiology and biotechnology , fibronectin , chemistry , extracellular matrix , mutant , cell adhesion , cell , medicine , biology , biochemistry , endocrinology , kidney , proteinuria , gene
Previous work showed that cell surface heparan sulfate (HS) glycosaminoglycans (GAG) modulate podocyte (podo) organization on the glomerular basement membrane (Kid. Int. 74: 289–299). This study examined the role of HSGAG sulfation in this process by podo‐specific deletion of NDST1, the enzyme responsible for N‐sulfation of HSGAG. A novel mutant mouse (2.5P‐Cre/NDST1 fl/fl ) and immortalized podo line (NDST1‐null) were developed using a Cre‐lox approach. The kidneys in mutant mice appeared normal compared to controls, the only measurable difference in routine LM studies was a slight glomerular hypertrophy in the mutant mice. Electron micrographs from mutant animals showed mild podo foot process effacement and abnormal podo attachment to Bowman's capsule, suggesting that podo‐matrix interactions were affected. NDST1‐null podo had a significantly decreased ability to adhere, spread, and migrate upon fibronectin compared to controls. Mutant podo also failed to assemble focal adhesions as efficiently as control cells. These results indicate that HSGAG sulfation is a critical mediator of cell surface proteoglycan (PG)‐matrix interaction, highlighting the importance of HSPGs in orchestrating podo cell behavior. This work is supported by: NIDDK RO1‐DK077860 Grant Funding Source : NDDK RO1‐ DK077860