title: Transgelin is a marker of repopulating mesangial cells after injury and promotes their proliferation and migration.
abstract: Mesangial cell (MC) migration is essential during glomerular repair and kidney development. The aim of the study was to identify marker/player for glomerular progenitor/reserve cells migrating into the glomerulus after MC injury and during glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2, 3, and 5 after induction of anti-Thy1 nephritis using Affymetrix microarray technology. Using self-organizing maps, transgelin was identified as a new marker for repopulating glomerular cells. Expression of transgelin during anti-Thy1 nephritis was investigated by northern blot, real-time PCR, western blot, and immunohistochemistry. Migration and proliferation assays using isolated MCs after transgelin knockdown by siRNA were performed to investigate the potential role of transgelin during glomerular repopulation. Transgelin mRNA was not detected in healthy glomeruli. It was strongly upregulated during the repopulation process starting on day 1, continued to be increased until day 5 and disappeared on day 7. Transgelin was specifically expressed at the edge of the migratory front during glomerular repopulation as indicated by transgelin/OX-7 double staining. Transgelin expression was similar in migrating vs non-migrating MCs in vitro. Blocking of transgelin expression by siRNA treatment resulted in inhibition of MC migration and proliferation. Transgelin was also expressed in MCs during glomerulogenesis and in biopsies from patients with IgA nephritis. In conclusion, transgelin in the kidney is upregulated in repopulating MCs in vivo and supports their migratory and proliferative repair response after injury.
authors.affiliation: Division of Nephropathology, University of Erlangen-Nürnberg, Erlangen, Germany. christoph.daniel@uk-erlangen.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.forename: Andrea
authors.initials: A
authors.lastname: Lüdke
authors.forename: Andrea
authors.initials: A
authors.lastname: Wagner
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Todorov
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
authors.forename: Christian
authors.initials: C
authors.lastname: Hugo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D050527:Mesangial Cells / Q000166:cytology*; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C051615:transgelin