Type 3 muscarinic acetylcholine receptor stimulation is a determinant of endothelial barrier function and adherens junctions integrity: role of protein-tyrosine phosphatase 1B |
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| Authors: | Zhou-Yang Jiao Jing Wu Chao Liu Bing Wen Wen-Zeng Zhao Xin-Ling Du |
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| Institution: | 1.Department of Cardiovascular Surgery, Xiehe Hospital, Huazhong University of Science and Technology, Wuhan 430022, China;2.Department of Cardiovascular Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;3.Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China |
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| Abstract: | The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and β-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and β-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase Cα (PKCα). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation. BMB Reports 2014; 47(10): 552-557] |
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| Keywords: | β -catenin M3R PTP1B VE-cadherin |
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