Calcineurin B1 subunit in human peripheral blood mononuclear cells and its role in idiopathic membranous nephropathy

Medicine (Baltimore). 2019 Apr;98(15):e15231. doi: 10.1097/MD.0000000000015231.

Abstract

The immune responses involved in the pathogenesis of idiopathic membranous nephropathy (IMN) have not been fully understood. Calcineurin, a key signaling enzyme in T-cell activation, may be implicated in IMN. The present study aimed to investigate the role of calcineurin B1 subunit (CnB1) in IMN and the potential mechanism.A total of 59 biopsy-proven IMN patients and 28 healthy controls were recruited. The CnB1 expression in human peripheral blood mononuclear cells (PBMCs) was assessed by Western blotting. Knockdown and overexpression of CnB1 in Jurkat T cell line were achieved by small interference RNA (siRNA) transfection and lentiviral transduction, respectively.It was found that PBMCs CnB1 expression was significantly increased in IMN patients (P = .002), but unrelated to the severity and prognosis of IMN. Knockdown of CnB1 in Jurkat cells inhibited the nuclear factor of activated T cells (NFAT)-regulated gene expression required for T-cell activation.Our study suggested the potential role of CnB1 in the occurrence of IMN. The mechanism maybe involved the effect of CnB1 on the T-cell activation mediated by calcineurin-NFAT signaling.

MeSH terms

  • Adult
  • Calcineurin / blood*
  • Calcineurin / genetics
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Glomerulonephritis, Membranous / blood*
  • Glomerulonephritis, Membranous / therapy
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Immunosuppression Therapy
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • NFATC Transcription Factors / metabolism
  • Prognosis
  • Severity of Illness Index

Substances

  • IL2 protein, human
  • Interleukin-2
  • NFATC Transcription Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Calcineurin