Li Gu1,2, Han-Min Liu3,4. 1. Department of Pediatric Pneumology, West China Second University Hospital, Sichuan University, Chengdu, China. 2. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Wuhou District, Chengdu, China. 3. Department of Pediatric Pneumology, West China Second University Hospital, Sichuan University, Chengdu, China. hanmin@vip.163.com. 4. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Wuhou District, Chengdu, China. hanmin@vip.163.com.
Abstract
BACKGROUND: Forkhead box M1 (FoxM1), a member of forkhead family, plays a key role in carcinogenesis, progression, invasion, metastasis and drug resistance. Based on the similarities between cancer and pulmonary arterial hypertension, studies on the roles and mechanisms of FoxM1 in pulmonary arterial hypertension have been increasing. This article aims to review recent advances in the mechanisms of signal transduction associated with FoxM1 in pulmonary arterial hypertension. DATA SOURCES: Articles were retrieved from PubMed and MEDLINE published after 1990, including-but not limited to-FoxM1 and pulmonary arterial hypertension. RESULTS: FoxM1 is overexpressed in pulmonary artery smooth muscle cells in both pulmonary arterial hypertension patients and animal models, and promotes pulmonary artery smooth muscle cell proliferation and inhibits cell apoptosis via regulating cell cycle progression. Multiple signaling molecules and pathways, including hypoxia-inducible factors, transforming growth factor-β/Smad, SET domain-containing 3/vascular endothelial growth factor, survivin, cell cycle regulatory genes and DNA damage response network, are reported to cross talk with FoxM1 in pulmonary arterial hypertension. Proteasome inhibitors are effective in the prevention and treatment of pulmonary arterial hypertension by inhibiting the expression and transcriptional activity of FoxM1. CONCLUSIONS: FoxM1 has a crucial role in the pathogenesis of pulmonary arterial hypertension and may represent a novel therapeutic target. But more details of interaction between FoxM1 and other signaling pathways need to be clarified in the future.
BACKGROUND:Forkhead box M1 (FoxM1), a member of forkhead family, plays a key role in carcinogenesis, progression, invasion, metastasis and drug resistance. Based on the similarities between cancer and pulmonary arterial hypertension, studies on the roles and mechanisms of FoxM1 in pulmonary arterial hypertension have been increasing. This article aims to review recent advances in the mechanisms of signal transduction associated with FoxM1 in pulmonary arterial hypertension. DATA SOURCES: Articles were retrieved from PubMed and MEDLINE published after 1990, including-but not limited to-FoxM1 and pulmonary arterial hypertension. RESULTS:FoxM1 is overexpressed in pulmonary artery smooth muscle cells in both pulmonary arterial hypertensionpatients and animal models, and promotes pulmonary artery smooth muscle cell proliferation and inhibits cell apoptosis via regulating cell cycle progression. Multiple signaling molecules and pathways, including hypoxia-inducible factors, transforming growth factor-β/Smad, SET domain-containing 3/vascular endothelial growth factor, survivin, cell cycle regulatory genes and DNA damage response network, are reported to cross talk with FoxM1 in pulmonary arterial hypertension. Proteasome inhibitors are effective in the prevention and treatment of pulmonary arterial hypertension by inhibiting the expression and transcriptional activity of FoxM1. CONCLUSIONS:FoxM1 has a crucial role in the pathogenesis of pulmonary arterial hypertension and may represent a novel therapeutic target. But more details of interaction between FoxM1 and other signaling pathways need to be clarified in the future.
Authors: Christophe Guignabert; Ly Tu; Morane Le Hiress; Nicolas Ricard; Caroline Sattler; Andrei Seferian; Alice Huertas; Marc Humbert; David Montani Journal: Eur Respir Rev Date: 2013-12
Authors: Il-Man Kim; Sneha Ramakrishna; Galina A Gusarova; Helena M Yoder; Robert H Costa; Vladimir V Kalinichenko Journal: J Biol Chem Date: 2005-04-06 Impact factor: 5.157
Authors: Zhiyu Dai; Maggie M Zhu; Yi Peng; Hua Jin; Narsa Machireddy; Zhijian Qian; Xianming Zhang; You-Yang Zhao Journal: Am J Respir Crit Care Med Date: 2018-09-15 Impact factor: 21.405
Authors: Florent Soubrier; Wendy K Chung; Rajiv Machado; Ekkehard Grünig; Micheala Aldred; Mark Geraci; James E Loyd; C Gregory Elliott; Richard C Trembath; John H Newman; Marc Humbert Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094