FAR2 is associated with kidney disease in mice and humans

Physiol Genomics. 2018 Aug 1;50(8):543-552. doi: 10.1152/physiolgenomics.00118.2017. Epub 2018 Apr 13.


Mesangial matrix expansion is an important process in the initiation of chronic kidney disease, yet the genetic factors driving its development are unknown. Our previous studies have implicated Far2 as a candidate gene associated with differences in mesangial matrix expansion between mouse inbred strains. Consistent with the hypothesis that increased expression of Far2 leads to mesangial matrix expansion through increased production of platelet-activating factor precursors, we show that FAR2 is capable of mediating de novo platelet-activating factor synthesis in vitro and driven by the transcription factor NKX3.2. We demonstrate that knockdown of Far2 in mice delays the progression of mesangial matrix expansion with at least six months (equivalent to ~15 yr in human). Furthermore, we show that increased FAR2 expression in human patients is associated with diabetic nephropathy, lupus nephritis, and IgA nephropathy. Taken together, these results highlight FAR2's role in the development of mesangial matrix expansion and chronic kidney disease.

Keywords: aging; kidney; mesangial matrix; mouse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aldehyde Oxidoreductases / genetics*
  • Aldehyde Oxidoreductases / metabolism
  • Animals
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / metabolism
  • Female
  • Glomerular Mesangium / metabolism*
  • Glomerular Mesangium / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Young Adult


  • FAR2 protein, human
  • Homeodomain Proteins
  • NKX3-2 protein, human
  • Transcription Factors
  • Aldehyde Oxidoreductases
  • FAR2 protein, mouse