Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

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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5 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)284-293
Number of pages10
JournalClinical and Experimental Nephrology
Volume17
Issue number2
DOIs
Publication statusPublished - 2013 Apr

Keywords

  • Epithelial-to-mesenchymal transition
  • Heme oxygenase-1
  • Peritoneal fibrosis

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

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  • Cite this

    Bang, K., Jeong, J., Shin, J. H., Kang, J. H., Kim, C. N., Yeom, H. J., Yoon, M. O., Yang, J., Ahn, C., Hwang, J. I., Park, M. Y., Kim, J. H., & Lee, K. W. (2013). Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells. Clinical and Experimental Nephrology, 17(2), 284-293. https://doi.org/10.1007/s10157-012-0699-y