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TNF superfamily: a growing saga of kidney injury modulators

Maria D Sanchez-Niño1, Alberto Benito-Martin, Sara Gonçalves

  • 1IIS- Fundación Jiménez Díaz, 28040 Madrid, Spain.

Mediators of Inflammation
|October 19, 2010
PubMed

Insights

Tumor necrosis factor (TNF) superfamily members are involved in kidney disease. Targeting these cytokines, like TNF-related apoptosis-inducing ligand (TRAIL) and TNF-like weak inducer of apoptosis (TWEAK), may offer new therapeutic strategies for kidney injury.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Members of the Tumor Necrosis Factor (TNF) superfamily play significant roles in kidney disease pathogenesis.
  • TNF and Fas ligand influence renal cell survival and inflammation, with therapeutic targeting showing promise in experimental models.
  • Increased expression of TNF-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin is observed in human diabetic nephropathy.

Purpose of the Study:

  • To elucidate the specific roles of TNF superfamily members, including TRAIL and TNF-like weak inducer of apoptosis (TWEAK), in kidney disease.
  • To investigate the signaling pathways activated by these cytokines in renal cells.
  • To evaluate the potential of targeting TNF superfamily cytokines for therapeutic intervention in kidney injury.

Main Methods:

  • Analysis of gene expression in human diabetic nephropathy.
  • In vitro studies on tubular cells and podocytes, including high-glucose environments.
  • Investigation of NF-kappaB signaling pathways (canonical and noncanonical) activated by TNF and TWEAK.
  • In vivo studies examining TWEAK's role in postnephrectomy compensatory proliferation and acute kidney injury.

Main Results:

  • TRAIL promotes apoptosis in tubular cells and podocytes, particularly under high-glucose conditions, while osteoprotegerin confers protection.
  • TWEAK induces inflammation and cell death or proliferation depending on the microenvironment.
  • TWEAK differentially activates NF-kappaB pathways, influencing the expression of chemokines (MCP-1, RANTES, CCL21, CCL19) and regulating renal cell proliferation or death in different injury contexts.

Conclusions:

  • TNF superfamily members are key regulators of renal cell fate and inflammation in kidney disease.
  • TRAIL and TWEAK exhibit distinct and context-dependent effects on renal cells, impacting apoptosis, proliferation, and inflammation.
  • Targeting multiple TNF superfamily cytokines presents a promising therapeutic avenue for managing kidney diseases.

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