Fra-2 is a novel candidate drug target expressed in the podocytes of lupus nephritis

Clin Immunol. 2018 Dec:197:179-185. doi: 10.1016/j.clim.2018.10.001. Epub 2018 Oct 5.

Abstract

Lupus nephritis (LN) is a common and devastating complication caused by systemic lupus erythematosus. In this study, we evaluated the expression and mechanism of Fos-related antigen 2 (Fra-2) in LN. The results showed that Fra-2 was significantly increased in kidney biopsies of LN patients compared with healthy controls and other kidney disease in glomerular podocytes. The MRL/lpr mouse strain is a murine model of lupus, and it was used to study the mechanisms of Fra-2 in LN. The results showed that Fra-2 was expressed in the glomerular podocytes. We investigated the effects of inflammatory stimuli on Fra-2 protein expression in the glomerular podocytes, and found that interferon gamma was most effective at increasing Fra-2 protein expression. Knockdown of Fra-2 using siRNA enhanced the protein expression of nephrin. Therefore, Fra-2 may be a specific drug target for podocyte injury in LN.

Keywords: Fra 2; Kidney injury; Lupus nephritis; MRL/lpr mice; Podocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Fos-Related Antigen-2 / drug effects
  • Fos-Related Antigen-2 / genetics*
  • Fos-Related Antigen-2 / metabolism*
  • Gene Knockdown Techniques
  • Glomerulonephritis, IGA / metabolism
  • Glomerulonephritis, Membranous / metabolism
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Humans
  • IgA Vasculitis / metabolism
  • Interferon-gamma / pharmacology
  • Lupus Nephritis / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred MRL lpr
  • Nephrosis, Lipoid / metabolism
  • Podocytes / metabolism*

Substances

  • Antiviral Agents
  • FOSL2 protein, human
  • Fos-Related Antigen-2
  • Fosl2 protein, mouse
  • Membrane Proteins
  • nephrin
  • Interferon-gamma