Abstract

Public Health Relevance

Previous work showed that lung injury activates a local tissue angiotensin system in pulmonary alveolar epithelial cells (AECs) and demonstrated that de novo synthesis of angiotensin (ANG) II is required for AEC apoptosis and subsequent lung fibrosis in animal models. An important component of this system that has not been studied well is angiotensin converting enzyme-2 (ACE-2), a carboxypeptidase that degrades ANGII to form ANG1-7, a heptapeptide that blocks ANGII action. This proposal is designed to begin elucidating the function(s) of ACE-2 and ANG1-7 in AEC survival in the context of lung fibrogenesis, and to begin defining the mechanisms by which ACE-2 is downregulated in experimental lung fibrosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL045136-21
Application #
7886790
Study Section
Lung Injury, Repair, and Remodeling Study Section (LIRR)
Program Officer
Lin, Sara
Project Start
1990-09-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
21
Fiscal Year
2010
Total Cost
$298,801
Indirect Cost

  Institution

Name
Michigan State University
Department
Physiology
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Abdul-Hafez, Amal; Mohamed, Tarek; Omar, Hanan et al. (2018) The renin angiotensin system in liver and lung: impact and therapeutic potential in organ fibrosis. J Lung Pulm Respir Res 5:
Ota, C; Gopallawa, I; Ivanov, V et al. (2017) Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors. J Lung Pulm Respir Res 4:
Gopallawa, Indiwari; Uhal, Bruce D (2016) Angiotensin-(1-7)/mas inhibits apoptosis in alveolar epithelial cells through upregulation of MAP kinase phosphatase-2. Am J Physiol Lung Cell Mol Physiol 310:L240-8
Gandhi, Chintan; Uhal, Bruce D (2016) Roles of the Angiotensin System in Neonatal Lung Injury and Disease. JSM Atheroscler 1:
Abdelwahab, Abdellatif; Gopallawa, Indiwari; Piasecki, Christopher C et al. (2016) Bleomycin-Induced Neonatal Lung Injury Requires the Autocrine Pulmonary Angiotensin System. Jacobs J Pulmonol 2:
Mohamed, Tarek L; Nguyen, Hang T; Abdul-Hafez, Amal et al. (2016) Prior hypoxia prevents downregulation of ACE-2 by hyperoxia in fetal human lung fibroblasts. Exp Lung Res 42:121-30
Oarhe, Chinyere I; Dang, Vinh; Dang, MyTrang et al. (2015) Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts. Pediatr Res 77:656-62
Gopallawa, Indiwari; Uhal, Bruce D (2014) Molecular and cellular mechanisms of the inhibitory effects of ACE-2/ANG1-7/Mas axis on lung injury. Curr Top Pharmacol 18:71-80
Dang, My-Trang T; Gu, Chenyang; Klavanian, Jeannie I et al. (2013) Angiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and Spanish IPF cohorts. Lung 191:353-60
Uhal, Bruce D; Dang, MyTrang; Dang, Vinh et al. (2013) Cell cycle dependence of ACE-2 explains downregulation in idiopathic pulmonary fibrosis. Eur Respir J 42:198-210

Showing the most recent 10 out of 16 publications