title: Involvement of infiltrating macrophage-derived activin A in the progression of renal damage in MRL-lpr mice.
abstract: Lupus nephritis is a life-threatening complication of systemic lupus erythematosus (SLE). Various growth factors, cytokines, and chemokines are implicated in the development of SLE. However, the pathophysiological processes involved in the development of lupus nephritis still remain unclear. In this study, we examined the involvement of activin A, a member of the transforming growth factor β (TGF-β) superfamily, in the progression of renal damage in lupus-prone MRL-lpr mice. Activin A was not expressed in the kidneys of control MRL-MpJ mice but was detectable in perivascular infiltrating cluster of differentiation 68 (CD68)-positive cells in the kidneys of MRL-lpr mice. Urinary activin A, which was also absent in MRL-MpJ mice, was detectable in MRL-lpr mice from 16 wk onward. Urinary activin A levels were significantly correlated with the number of perivascular inflammatory cell layers, the number of crescentic glomeruli, and the percentage of Elastica van Gieson (EVG)-positive fibrotic areas, but not with urinary protein levels or serum activin A. When activin action was blocked in vivo by the intraperitoneal administration of an activin antagonist, follistatin, the number of crescentic glomeruli, percentage of EVG-positive fibrotic areas, CD68-positive cell infiltration, and proteinuria were significantly reduced in a dose-dependent manner. These data suggest that infiltrating macrophage-derived activin A is involved in the progression of renal damage in MRL-lpr mice.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Anastasie Tshilela
authors.initials: AT
authors.lastname: Kadiombo
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan amaesima@gunma-u.ac.jp.
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kayakabe
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.affiliation: Department of Medicine and Clinical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D038681:Follistatin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D028341:Activins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D038681:Follistatin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C422405:activin A
keywords: activin; lupus nephritis; urinary biomarker