Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria

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 i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ming-Fo Hsu, Ahmed Bettaieb, Yoshihiro Ito, James Graham, Peter J. Havel, Fawaz G. Haj
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/596de7c5fb144f74bc697024e074dc19
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:596de7c5fb144f74bc697024e074dc19
record_format	dspace
spelling	oai:doaj.org-article:596de7c5fb144f74bc697024e074dc192021-12-02T16:08:23ZProtein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria10.1038/s41598-017-00564-32045-2322https://doaj.org/article/596de7c5fb144f74bc697024e074dc192017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00564-3https://doaj.org/toc/2045-2322Abstract 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-1β, TNFα, INFγ 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-κB 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.Ming-Fo HsuAhmed BettaiebYoshihiro ItoJames GrahamPeter J. HavelFawaz G. HajNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming-Fo Hsu Ahmed Bettaieb Yoshihiro Ito James Graham Peter J. Havel Fawaz G. Haj Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
description	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-1β, TNFα, INFγ 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-κB 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.
format	article
author	Ming-Fo Hsu Ahmed Bettaieb Yoshihiro Ito James Graham Peter J. Havel Fawaz G. Haj
author_facet	Ming-Fo Hsu Ahmed Bettaieb Yoshihiro Ito James Graham Peter J. Havel Fawaz G. Haj
author_sort	Ming-Fo Hsu
title	Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
title_short	Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
title_full	Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
title_fullStr	Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
title_full_unstemmed	Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
title_sort	protein tyrosine phosphatase shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/596de7c5fb144f74bc697024e074dc19
work_keys_str_mv	AT mingfohsu proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria AT ahmedbettaieb proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria AT yoshihiroito proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria AT jamesgraham proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria AT peterjhavel proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria AT fawazghaj proteintyrosinephosphataseshp2deficiencyinpodocytesattenuateslipopolysaccharideinducedproteinuria
_version_	1718384530096652288

Protein tyrosine phosphatase Shp2 deficiency in podocytes attenuates lipopolysaccharide-induced proteinuria

Ejemplares similares