HDAC10 promotes angiogenesis in endothelial cells through the PTPN22/ERK axis
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Baoyu Duan1, Dan Ye1, Songcheng Zhu1, Wenwen Jia1, Chenqi Lu2, Guiying Wang1, Xudong Guo1, Yangyang Yu1, Chuanyue Wu3,4 and Jiuhong Kang1
1Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China
2Department of Biostatistics and Computational Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
3Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China
4Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
Jiuhong Kang, email: firstname.lastname@example.org
Chuanyue Wu, email: email@example.com
Keywords: angiogenesis, histone deacetylase 10 (HDAC10), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ERK1/2 phosphorylation, tube formation
Received: February 27, 2017 Accepted: April 12, 2017 Published: May 24, 2017
Angiogenesis is crucially involved in many physiological and pathological processes including tumor growth, but the molecular mechanisms regulating angiogenesis are incompletely understood. In this study, we investigated the functions and mechanism of histone deacetylase 10 (HDAC10), a member of the HDAC II family, in regulation of angiogenesis. HDAC10 overexpression in human umbilical vein endothelial cells (HUVECs) promoted tube formation, whereas depletion of HDAC10 from HUVECs inhibited tube formation in vitro and in vivo. Mechanistically, HDAC10 overexpression increased extracellular-regulated kinase 1/2 (ERK1/2) activation, whereas depletion of HDAC10 inhibited ERK1/2 activation. Finally, HDAC10 promoted ERK1/2 phosphorylation by deacetylating the promoter of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and inhibiting the expression of PTPN22, which is a negative regulator of ERK phosphorylation. Collectively, our results identify HDAC10 as a key regulator of angiogenesis and reveal that HDAC10 functions in this process by binding and deacetylating the PTPN22 promoter and subsequently inhibiting PTPN22 expression, which in turn increases ERK1/2 phosphorylation. Our studies suggest that HDAC10 is a potential target for therapeutic intervention to inhibit angiogenesis and tumor growth.
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