Document Detail


Enhancer of zeste homolog 2 induces pulmonary artery smooth muscle cell proliferation.
MedLine Citation:
PMID:  22662197     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Pulmonary Arterial Hypertension (PAH) is a progressively devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. The proliferation of cancer cells is mediated by increased expression of Enhancer of Zeste Homolog 2 (EZH2), a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes. However, the role of EZH2 in PAH has not been studied. In this study, it is hypothesized that EZH2 could play a role in the proliferation of PASMCs.
METHODS: In the present study, the expression patterns of EZH2 were investigated in normal and hypertensive mouse PASMCs. The effects of EZH2 overexpression on the proliferation of human PASMCs were tested. PASMCs were transfected with EZH2 or GFP using nucleofector system. After transfection, the cells were incubated for 48 hours at 37°C. Proliferation and cell cycle analysis were performed using flow cytometry. Apoptosis of PASMCs was determined using annexin V staining and cell migration was tested by wound healing assay.
RESULTS: EZH2 protein expression in mouse PASMCs were correlated with an increase in right ventricular systolic pressure and Right Ventricular Hypertrophy (RVH). The overexpression of EZH2 in human PASMCs enhances proliferation, migration, and decrease in the rate of apoptosis when compared to GFP-transfected cells. In the G2/M phase of the EZH2 transfected cells, there was a 3.5 fold increase in proliferation, while there was a significant decrease in the rate of apoptosis of PASMCs, when compared to control.
CONCLUSION: These findings suggest that EZH2 plays a role in the migration and proliferation of PASMCs, which is a major hallmark in PAH. It also suggests that EZH2 could play a role in the development of PAH and can serve as a potential target for new therapies for PAH.
Authors:
Salman A Aljubran; Ruan Cox; Prasanna Tamarapu Parthasarathy; Gurukumar Kollongod Ramanathan; Venugopal Rajanbabu; Huynh Bao; Shyam S Mohapatra; Shyam M Mohapatra; Richard Lockey; Narasaiah Kolliputi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-25
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-04     Completed Date:  2012-12-13     Revised Date:  2013-08-07    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e37712     Citation Subset:  IM    
Affiliation:
Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia
Apoptosis / genetics
Cell Movement / genetics
Cell Proliferation
Disease Models, Animal
Disease Progression
Gene Expression
Humans
Hypertension, Pulmonary / genetics,  metabolism
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular / metabolism*
Myocytes, Smooth Muscle / metabolism*
Phenotype
Polycomb Repressive Complex 2 / genetics,  metabolism*
Pulmonary Artery / metabolism*
Grant Support
ID/Acronym/Agency:
R01 HL105932/HL/NHLBI NIH HHS; R01 HL105932/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 2.1.1.43/EZH2 protein, human; EC 2.1.1.43/Polycomb Repressive Complex 2
Comments/Corrections
Erratum In:
PLoS One. 2012;7(8). doi: 10.1371/annotation/8580b50a-1556-4c86-aeb6-a88af839297a
Note: Mohapatra, Shyam M [corrected to Mohapatra, Shyam S]

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