Involvement of infiltrating macrophage-derived activin A in the progression of renal damage in MRL-lpr mice

Am J Physiol Renal Physiol. 2017 Feb 1;312(2):F297-F304. doi: 10.1152/ajprenal.00191.2016. Epub 2016 Nov 23.


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.

Keywords: activin; lupus nephritis; urinary biomarker.

MeSH terms

  • Activins / metabolism*
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Biomarkers / urine
  • Disease Progression
  • Female
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Follistatin / pharmacology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred MRL lpr
  • Proteinuria / metabolism
  • Proteinuria / pathology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD68 antigen, human
  • Follistatin
  • activin A
  • Activins