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HGF and BMP-7 ameliorate high glucose-induced epithelial-to-mesenchymal transition of peritoneal mesothelium

Title
HGF and BMP-7 ameliorate high glucose-induced epithelial-to-mesenchymal transition of peritoneal mesothelium
Authors
Yu M.-A.Shin K.-S.Kim J.H.Kim Y.-I.Chung S.S.Park S.-H.Kim Y.-L.Kang D.-H.
Ewha Authors
강덕희정순섭김용일
SCOPUS Author ID
강덕희scopus; 정순섭scopus; 김용일scopus
Issue Date
2009
Journal Title
Journal of the American Society of Nephrology
ISSN
1046-6673JCR Link
Citation
vol. 20, no. 3, pp. 567 - 581
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Over time, peritoneal dialysis results in functional and structural alterations of the peritoneal membrane, but the underlying mechanisms and whether these changes are reversible are not completely understood. Here, we studied the effects of high levels of glucose, which are found in the dialysate, on human peritoneal mesothelial cells (HPMCs). We found that high concentrations of glucose induced epithelial- to-mesenchymal transition (EMT) of HPMC, suggested by decreased expression of E-cadherin and increased expression of α-smooth muscle actin, fibronectin, and type I collagen and by increased cell migration. Normalization of glucose concentration on day 2 reversed the phenotypic transformation, but the changes were irreversible after 7 d of stimulation with high glucose. In addition, exposure of HPMC to high glucose resulted in a decreased expression of the antifibrotic cytokines, hepatocyte growth factor (HGF) and bone morphogenic protein 7 (BMP-7). Exogenous treatment with HGF resulted in a dosage-dependent prevention of high glucose-induced EMT. Both BMP-7 peptide and gene transfection with an adenoviral vector of BMP-7 also protected HPMCs from EMT. Furthermore, adenoviral BMP-7 transfection decreased peritoneal EMT and ameliorated peritoneal thickening in an animal model of peritoneal dialysis. In summary, high concentrations of glucose induce a reversible EMT of HPMCs, associated with decreased production of HGF and BMP-7. Treatment of HPMCs with HGF or BMP-7 blocks high glucose-induced EMT, and BMP-7 ameliorates peritoneal fibrosis in an animal model of peritoneal dialysis. Copyright © 2009 by the American Society of Nephrology.
DOI
10.1681/ASN.2008040424
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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