Nakahara M, Nishio M, Saeki K, Yuo A, Saeki K. p38 mitogen-activated protein kinase regulates type-I vs type-II phenotyping of human vascular endothelial cells. World J Transl Med 2015; 4(3): 101-112 [DOI: 10.5528/wjtm.v4.i3.101]
Corresponding Author of This Article
Kumiko Saeki, MD, PhD, Division Chief, Department of Disease Control, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Tokyo 162-8655, Japan. saeki@ri.ncgm.go.jp
Research Domain of This Article
Research & Experimental Medicine
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Masako Nakahara, Miwako Nishio, Akira Yuo, Kumiko Saeki, Department of Disease Control, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Koichi Saeki, Section of Cell Engineering, Department of Basic Research, DNAVEC Center, ID Pharma Co., Ltd., Ibaraki 300-2611, Japan
Kumiko Saeki, PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan
Author contributions: Nakahara M and Nishio M performed the experiments and analyzed the data; Saeki K constructed viral vectors; Yuo A designed and coordinated the research; Saeki K designed the research, constructed viral vectors and wrote the paper.
Supported by A Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan, No. KHD1017; and by that from JST, PRESTO.
Institutional review board statement: The study was performed after having received an approval by the Japanese Government and the institutional review board of National Center for Global Health and Medicine.
Conflict-of-interest statement: None of the authors has any potential financial conflict of interest related to this manuscript.
Data sharing statement: Technical appendix and dataset are available from the corresponding author (saeki@ri.ncgm.go.jp).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kumiko Saeki, MD, PhD, Division Chief, Department of Disease Control, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo 162-8655, Tokyo 162-8655, Japan. saeki@ri.ncgm.go.jp
Telephone: +81-3-32027181 Fax: +81-3-32027364
Received: June 23, 2015 Peer-review started: June 29, 2015 First decision: August 16, 2015 Revised: September 3, 2015 Accepted: December 1, 2015 Article in press: December 2, 2015 Published online: December 12, 2015 Processing time: 175 Days and 0.7 Hours
Core Tip
Core tip: We previously reported that human vascular endothelial cells (VECs) are categorized into two types by their effects on the proliferation of vascular smooth muscle cells and the expressions of regulator of G-protein signaling 5 (RGS5): Pro-proliferative RGS5high (type-I) and anti-proliferative RGS5low (type-II) VECs. Performing proteomic kinase assays and inhibitor studies, we show here that p38 mitogen-activated protein kinase (p38 MAPK) is the crucial kinase that determines VEC phenotyping at the downstream of RGS5. Not only RGS5 overexpression suppressed p38 MAPK activities but also p38 MAPK inhibitions up-regulated RGS5 expression, indicating that “RGS5 induction” and “p38 MAPK inhibition” creates a vicious cycle in “type-II to type-I” conversions of human VECs.
