title: Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Internal Medicine, School of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Kitae
authors.initials: K
authors.lastname: Bang
authors.forename: Jinuk
authors.initials: J
authors.lastname: Jeong
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Ju Hyung
authors.initials: JH
authors.lastname: Kang
authors.forename: Chang Nam
authors.initials: CN
authors.lastname: Kim
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Yeom
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Yoon
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Hwang
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Park
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kang Wook
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005355:Fibrosis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D053773:Transforming Growth Factor beta1; D006427:Hemin; D051547:Heme Oxygenase-1; D005947:Glucose