title: HCaRG accelerates tubular repair after ischemic kidney injury.
abstract: The repair of the kidney after ischemia/reperfusion injury involves proliferation of proximal tubular epithelial cells as well as cell migration and differentiation. Immediately after reperfusion, expression of hypertension-related calcium-regulated gene (HCaRG/COMMD5) decreases, but its expression increases even higher than baseline during repair. HCaRG inhibits proliferation and accelerates wound healing and differentiation in cultured cells, but whether HCaRG can stimulate renal repair after ischemia/reperfusion injury is unknown. Here, transgenic mice overexpressing human HCaRG survived longer and recovered renal function faster than littermate controls after ischemia/reperfusion (64% versus 25% survival at 7 days). Proliferation of proximal tubular epithelial cells stopped earlier after ischemia/reperfusion injury, E-cadherin levels recovered more rapidly, and vimentin induction abated faster in transgenic mice. HCaRG overexpression also reduced macrophage infiltration and inflammation after injury. Taken together, these data suggest that HCaRG accelerates repair of renal proximal tubules by modulating cell proliferation of resident tubular epithelial cells and by facilitating redifferentiation.
authors.affiliation: Centre de Recherche, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Julie L
authors.initials: JL
authors.lastname: Lavoie
authors.forename: Louis
authors.initials: L
authors.lastname: Gaboury
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
mesh_terms: D058186:Acute Kidney Injury / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004285:Dogs; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009393:Nephritis / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology*; D015427:Reperfusion Injury / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D015996:Survival Rate; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485926:COMMD5 protein, human; D009687:Nuclear Proteins