TITLE

Inhibition of Protein Tyrosine Phosphatase Improves Angiogenesis via Enhancing Ang-1/Tie-2 Signaling in Diabetes

AUTHOR(S)
Jian-Xiong Chen; Qinhui Tuo; Duan-Fang Liao; Heng Zeng
PUB. DATE
January 2012
SOURCE
Experimental Diabetes Research;2012, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Diabetes is associated with impairment of angiogenesis such as reduction of myocardial capillary formation. Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1 )/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation. In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang- 1/Tie-2 angiogenic signaling and angiogenesis. SHP-1 expression was significantly increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose (HG, 30mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.
ACCESSION #
84957822

 

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