title: Involvement of epimorphin in the repair of experimental renal fibrosis in mice.
abstract: Interaction between epithelial cells and mesenchymal cells is essential in normal organ morphogenesis and in tissue repair after injury. Epimorphin, a mesenchymal protein that regulates epithelial morphogenesis through epithelial-mesenchymal interactions, has recently attracted attention as an important modulator of tissue repair. In this study we analyzed the role of epimorphin in renal fibrosis. We first found a progressive increase in epimorphin expression corresponding to the progression of renal fibrosis in mice with unilateral ureteral obstruction (UUO). To determine whether this expression has a role in the repair or progression of renal fibrosis, we analyzed a model of renal fibrosis repair, the UUO-release (UUO-R) model. Epimorphin expression was increased at 3 and 7 days after the UUO-R rather than on the day of release, but was decreased at 21 days after the release. Inhibition of endogenous epimorphin with anti-epimorphin antibody (MC-1) significantly delayed the repair of fibrosis. When compared with normal-IgG-injected mice, MC-1-injected mice showed significantly decreased renal matrix metalloproteinase (MMP)-2 and MMP-9 expressions by western blotting and increased expression of TGF-beta and collagen-I mRNA by real-time RT-PCR. Recombinant epimorphin induced prominent increases in MMP-2 and MMP-9 activities in the culture media of renal interstitial fibroblasts in vitro. These findings indicate that epimorphin has a pivotal role in the repair of renal fibrosis by modulating both extracellular matrix (ECM) degradation and its production.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Saitama, Japan.
authors.forename: Muneharu
authors.initials: M
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.forename: Keishi
authors.initials: K
authors.lastname: Higashi
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Kushiyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamakami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hirai
authors.forename: Kojiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Toshitake
authors.initials: T
authors.lastname: Hyodo
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018450:Disease Progression; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D014513:Ureter / Q000293:injuries / Q000473:pathology; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology*
chemical_list: D000906:Antibodies; C504582:Epim protein, mouse; D008562:Membrane Glycoproteins