Gene Expression of TWEAK/Fn14 and IP-10/CXCR3 in Glomerulus and Tubulointerstitium of Patients With Lupus Nephritis

Nephrology (Carlton). 2011 May;16(4):426-32. doi: 10.1111/j.1440-1797.2011.01449.x.

Abstract

Aim: The role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 and interferon-inducible protein (IP-10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied.

Methods: The mRNA expression of TWEAK, Fn14, IP-10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls.

Results: As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = -0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = -0.447; P = 0.029).

Conclusion: In patients with lupus nephritis, there is an increase in intra-renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra-renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP-10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Chemokine CXCL10 / genetics*
  • Creatinine / blood
  • Cytokine TWEAK
  • Female
  • Gene Expression Regulation
  • Hong Kong
  • Humans
  • Kidney Glomerulus / chemistry*
  • Kidney Glomerulus / pathology
  • Kidney Tubules / chemistry*
  • Kidney Tubules / pathology
  • Lupus Nephritis / blood
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / pathology
  • Male
  • Middle Aged
  • Proteinuria / genetics
  • Proteinuria / pathology
  • RNA, Messenger / analysis
  • Receptors, CXCR3 / genetics*
  • Receptors, Tumor Necrosis Factor / genetics*
  • Severity of Illness Index
  • TWEAK Receptor
  • Tumor Necrosis Factors / genetics*

Substances

  • Biomarkers
  • CXCL10 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Cytokine TWEAK
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TNFSF12 protein, human
  • TWEAK Receptor
  • Tumor Necrosis Factors
  • Creatinine