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Publication
Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates
lipopolysaccharide-induced proteinuria.
Authors Hsu MF, Bettaieb A, Ito Y, Graham J, Havel PJ, Haj FG
Submitted By Submitted Externally on 5/1/2017
Status Published
Journal Scientific reports
Year 2017
Date Published 3/1/2017
Volume : Pages 7 : 461
PubMed Reference 28352079
Abstract Podocytes are specialized epithelial cells that play a significant role in
maintaining the integrity of the glomerular filtration barrier and preventing
urinary protein leakage. We investigated the contribution of protein tyrosine
phosphatase Shp2 to lipopolysaccharide (LPS)-induced renal injury. We report
increased Shp2 expression in murine kidneys and cultured podocytes following an
LPS challenge. To determine the role of podocyte Shp2 in vivo, we generated
podocyte-specific Shp2 knockout (pod-Shp2 KO) mice. Following administration of
LPS, pod-Shp2 KO mice exhibited lower proteinuria and blood urea nitrogen
concentrations than controls indicative of preserved filter integrity. In
addition, renal mRNA and serum concentrations of inflammatory cytokines IL-1ß,
TNFa, INF? and IL-12 p70 were significantly decreased in LPS-treated knockout
mice compared with controls. Moreover, the protective effects of podocyte Shp2
deficiency were associated with decreased LPS-induced NF-?B and MAPK activation,
nephrin phosphorylation and attenuated endoplasmic reticulum stress. These
effects were recapitulated in differentiated E11 murine podocytes with
lentiviral-mediated Shp2 knockdown. Furthermore, Shp2 deficient podocytes
displayed reduced LPS-induced migration in a wound healing assay. These findings
identify Shp2 in podocytes as a significant contributor to the signaling events
following LPS challenge and suggest that inhibition of Shp2 in podocytes may
present a potential therapeutic target for podocytopathies.




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