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Publication
Protein tyrosine phosphatase 1B deficiency in podocytes mitigates
hyperglycemia-induced renal injury.
Authors Ito Y, Hsu MF, Bettaieb A, Koike S, Mello A, Calvo-Rubio M, Villalba JM, Haj FG
Submitted By Submitted Externally on 11/27/2017
Status Published
Journal Metabolism: clinical and experimental
Year 2017
Date Published 11/1/2017
Volume : Pages 76 : 56 - 69
PubMed Reference 28987240
Abstract Diabetic nephropathy is one of the most devastating complications of diabetes,
and growing evidence implicates podocyte dysfunction in disease pathogenesis.
The objective of this study was to investigate the contribution of protein
tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal
injury., To determine the in vivo function of PTP1B in podocytes we generated
mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO).
Kidney functions were determined in control and pod-PTP1B KO mice under
normoglycemia and high-fat diet (HFD)- and streptozotocin (STZ)-induced
hyperglycemia., PTP1B expression increased in murine kidneys following HFD and
STZ challenges. Under normoglycemia control and pod-PTP1B KO mice exhibited
comparable renal functions. However, podocyte PTP1B disruption attenuated
hyperglycemia-induced albuminuria and renal injury and preserved glucose
control. Also, podocyte PTP1B disruption was accompanied with improved renal
insulin signaling and enhanced autophagy with decreased inflammation and
fibrosis. Moreover, the beneficial effects of podocyte PTP1B disruption in vivo
were recapitulated in E11 murine podocytes with lentiviral-mediated PTP1B
knockdown. Reconstitution of PTP1B in knockdown podocytes reversed the enhanced
insulin signaling and autophagy suggesting that they were likely a consequence
of PTP1B deficiency. Further, pharmacological attenuation of autophagy in PTP1B
knockdown podocytes mitigated the protective effects of PTP1B deficiency., These
findings demonstrate that podocyte PTP1B deficiency attenuates
hyperglycemia-induced renal damage and suggest that PTP1B may present a
therapeutic target in renal injury.




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