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Title: Rac1-PAK2 pathway is essential for zebrafish heart regeneration

Abstract

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.

Authors:
 [1];  [2]; ;  [1]
  1. State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203 (China)
  2. Center for Reproduction and Genetics, Suzhou Municipal Hospital, Jiangsu 215002 (China)
Publication Date:
OSTI Identifier:
22596331
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 472; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; HEART; INHIBITION; INJURIES; MOLECULES; PHOSPHOTRANSFERASES; REGENERATION; SERINE; THREONINE

Citation Formats

Peng, Xiangwen, He, Quanze, Li, Guobao, Ma, Jinmin, Zhong, Tao P., E-mail: taozhongfudan@yahoo.com, and Department of Medicine, Vanderbilt University School of Medicine, TN 37232. Rac1-PAK2 pathway is essential for zebrafish heart regeneration. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.03.011.
Peng, Xiangwen, He, Quanze, Li, Guobao, Ma, Jinmin, Zhong, Tao P., E-mail: taozhongfudan@yahoo.com, & Department of Medicine, Vanderbilt University School of Medicine, TN 37232. Rac1-PAK2 pathway is essential for zebrafish heart regeneration. United States. doi:10.1016/J.BBRC.2016.03.011.
Peng, Xiangwen, He, Quanze, Li, Guobao, Ma, Jinmin, Zhong, Tao P., E-mail: taozhongfudan@yahoo.com, and Department of Medicine, Vanderbilt University School of Medicine, TN 37232. Fri . "Rac1-PAK2 pathway is essential for zebrafish heart regeneration". United States. doi:10.1016/J.BBRC.2016.03.011.
@article{osti_22596331,
title = {Rac1-PAK2 pathway is essential for zebrafish heart regeneration},
author = {Peng, Xiangwen and He, Quanze and Li, Guobao and Ma, Jinmin and Zhong, Tao P., E-mail: taozhongfudan@yahoo.com and Department of Medicine, Vanderbilt University School of Medicine, TN 37232},
abstractNote = {P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.},
doi = {10.1016/J.BBRC.2016.03.011},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 472,
place = {United States},
year = {2016},
month = {4}
}