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Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.
MedLine Citation:
PMID:  23150184     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells has been regarded as an early mechanism of peritoneal fibrosis. A substantial and rapidly growing literature indicates that HO-1 provides the provenance for pathways that can interrupt virtually all major mechanisms of tissue injury. The effects of HO-1 expression on EMT, which plays a critical role in the development of peritoneal membrane (PM) fibrosis, are unknown and its roles in peritoneal fibrosis has not been studied, yet. METHODS: A piece of human omentum obtained from consenting patients undergoing elective abdominal surgery was used for study. We treated the human peritoneal mesothelial cells (HPMCs) with high glucose solution and HO-1 inducer (hemin, 10 μmol/L). To further investigate the pure effect of HO-1 on EMT of mesothelium, gene transfer of recombinant Adenovirus-harboring human HO-1 (Adv-HO-1 gene) to HPMCs was done. RESULTS: Exposure of HPMCs to HG solution resulted in an increase of the expression of mesenchymal markers such as α-smooth muscle actin (α-SMA) and was associated with a decrease in the expression of epithelial markers, E-cadherin. HO-1 protein expression was decreased in the same situation. Treatment of HPMCs with HO-1 inducer, hemin showed a dosage-dependent amelioration of HG induced changes in markers of EMT with increase of expression of HO-1. Human HO-1 gene transfection resulted in a significant increase in HO-1 expression and ameliorated HG-induced changes in expression of E-cadherin and α-SMA. CONCLUSION: Taken together, our results suggest that HO-1 has a critical role in the modulation of peritoneal fibrosis, and, more important, the suppression of EMT. This study is the first to show the beneficial effect of HO-1 on reversing EMT in MC.
Authors:
Kitae Bang; Jinuk Jeong; Jong Ho Shin; Ju Hyung Kang; Chang Nam Kim; Hye-Jung Yeom; Myeong Ok Yoon; Jaeseok Yang; Curie Ahn; Jong-Ik Hwang; Mee Young Park; Joo-Heon Kim; Kang Wook Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Clinical and experimental nephrology     Volume:  -     ISSN:  1437-7799     ISO Abbreviation:  Clin. Exp. Nephrol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709923     Medline TA:  Clin Exp Nephrol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, School of Medicine, Eulji University, Daejeon, Republic of Korea.
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