The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB.

@article{Moreno2011TheIC,
  title={The inflammatory cytokines TWEAK and TNF$\alpha$ reduce renal klotho expression through NF$\kappa$B.},
  author={Juan Antonio Moreno and Mar{\'i}a Concepci{\'o}n Izquierdo and Maria Dolores S{\'a}nchez-Ni{\~n}o and Beatriz Suarez-Alvarez and Carlos L{\'o}pez-Larrea and Aniela Jakubowski and Juli{\`a} Blanco and Rafael Ram{\'i}rez and Rafael Selgas and Marta Ru{\'i}z-Ortega and Jesus Egido and Alberto Ortiz and Ana Bel{\'e}n Sanz},
  journal={Journal of the American Society of Nephrology : JASN},
  year={2011},
  volume={22 7},
  pages={
          1315-25
        }
}
Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-like phenotype, including vascular injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice, exogenous administration of… 
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The inflammatory cytokine TWEAK decreases PGC-1α expression and mitochondrial function in acute kidney injury.
TLDR
TWEAK decreases PGC-1α and target gene expression in tubular cells in vivo and in vitro and Approaches that preserve mitochondrial function during kidney injury may be therapeutic for AKI.
Out of the TWEAKlight: Elucidating the Role of Fn14 and TWEAK in Acute Kidney Injury.
Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide-induced acute kidney injury
TLDR
Klotho is enriched in macrophages and Klotho preservation by Rhein attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation and possesses promising potentials in the clinical treatment of renal inflammatory disorders.
SOCS-1 is involved in TNF-α-induced mitochondrial dysfunction and apoptosis in renal tubular epithelial cells.
TWEAK and the progression of renal disease: clinical translation.
  • A. SanzM. C. Izquierdo A. Ortiz
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2014
TLDR
The nephroprotective effect of TWEAK or Fn14 targeting in immune-mediated kidney injury is the result of protection from TWEak-induced injury of renal intrinsic cells, not from interference with the immune response.
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and kidney disease
TLDR
It is suggested that TWEAK targeting has clinical potential in kidney injury of immune and nonimmune origin and Nanomolecules and inhibitors of epidermal growth factor receptor pathway may also protect from the adverse effects of T WEAK in the kidney.
Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis.
Bcl3: a regulator of NF-κB inducible by TWEAK in acute kidney injury with anti-inflammatory and antiapoptotic properties in tubular cells
TLDR
Truly therapeutic upregulation of Bcl3 activity should be explored in kidney disease because it has advantages over chemical inhibitors of NF-κB that are known to prevent inflammatory responses but can also sensitize the cells to apoptosis.
PGC1α Plays a Critical Role in TWEAK–Induced Cardiac Dysfunction
TLDR
The data suggest that TWEAK induces cardiac dysfunction via downregulation of PGC1α, through FN14-TRAF2-NFκB-dependent signaling pathways, which may serve as novel therapeutic strategies for cardiomyopathy and heart failure.
NFκBiz protein downregulation in acute kidney injury: Modulation of inflammation and survival in tubular cells.
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