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World J Respirol. Mar 28, 2015; 5(1): 40-46
Published online Mar 28, 2015. doi: 10.5320/wjr.v5.i1.40
Role of p53 in lung tissue remodeling
Shiro Mizuno, Harm Jan Bogaard, Takeshi Ishizaki, Hirohisa Toga
Shiro Mizuno, Takeshi Ishizaki, Hirohisa Toga, Division of Respiratory Medicine, Kanazawa Medical University, Ishikawa 920-0263, Japan
Harm Jan Bogaard, Department of Pulmonary Medicine, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
Author contributions: Mizuno S and Bogaard HJ wrote the paper; Ishizaki T and Toga H supervised the writing of the paper.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, No. 24591144.
Conflict-of-interest: None of the authors has any conflict of interest to disclose.
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: Shiro Mizuno, MD, PhD, Associate Professor, Division of Respiratory Medicine, Kanazawa Medical University, 1-1 Daigaku Uchinada-cho Kahoku-gun, Ishikawa 920-0265, Japan. shirotan@kanazawa-med.ac.jp
Telephone: +81-776-2188157 Fax: +81-776-2860980
Received: September 24, 2014
Peer-review started: September 26, 2014
First decision: November 19, 2014
Revised: December 6, 2014
Accepted: December 18, 2014
Article in press: December 20, 2014
Published online: March 28, 2015
Abstract

The tumor suppressor gene p53 regulates a wide range of cellular processes including cell cycle progression, proliferation, apoptosis and tissue development and remodeling. Lung cell apoptosis and tissue remodeling have critical roles in many lung diseases. Abnormal proliferation or resistance to apoptosis of lung cells will lead to structural changes of many lung tissues, including the pulmonary vascular wall, small airways and lung parenchyma. Among the many lung diseases caused by vascular cell apoptosis and tissue remodeling are chronic obstructive pulmonary disease, bronchial asthma and pulmonary arterial hypertension. Recent advances in biology and medicine have provided new insights and have resulted in new therapeutic strategies for tissue remodeling in human and animal models. This review is focused on lung disease susceptibility associated with the p53 pathway and describes molecular mechanisms upstream and downstream of p53 in lung tissue remodeling. Improved understanding of structural changes associated with pulmonary vascular remodeling and lung cell apoptosis induced by the p53 pathway may new provide therapeutic targets.

Keywords: Chronic obstructive pulmonary disease, Pulmonary hypertension, Asthma, p21, Mouse double minute 2 homolog

Core tip: The activated p53 protein and its associated pathway play a pivotal role in tissue remodeling in chronic obstructive pulmonary disease, asthma and pulmonary hypertension. p53 protein regulates numerous genes and proteins associated with cell cycle arrest and apoptosis. In response to oxidative stress or hypoxia, p53 can become stabilized and activate signal transduction towards lung tissue remodeling and functional loss.