title: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and kidney disease.
abstract: OBJECTIVE
  The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) cytokine has been linked to kidney injury by functional studies in experimental animals, and has biomarker potential in kidney disease.
  
  
  RESULTS
  TWEAK was known to promote tubular cell injury and kidney inflammation. Recent studies have expanded these observations, identifying additional targets of TWEAK relevant to kidney injury. Thus, TWEAK upregulates the chemokine and cholesterol scavenger receptor CXCL16 and downregulates the antiaging and antifibrotic molecule Klotho in tubular cells. Furthermore, fibrogenic TWEAK actions on renal fibroblasts were described. TWEAK or factor-inducible molecule 14 targeting decreased the kidney fibrosis resulting from immune and nonimmune kidney injury induced by transient tubular or glomerular insults or by persistent urinary tract obstruction. TWEAK might also contribute to the link between chronic kidney disease and kidney cancer, as suggested by its role in other genitourinary cancers. Progress has also been made in TWEAK targeting. A phase I clinical trial showed that TWEAK targeting is well tolerated in humans, and an ongoing trial is exploring efficacy in lupus nephritis. Nanomolecules and inhibitors of epidermal growth factor receptor pathway may also protect from the adverse effects of TWEAK in the kidney.
  
  
  CONCLUSIONS
  These findings suggest that TWEAK targeting has clinical potential in kidney injury of immune and nonimmune origin.
authors.affiliation: aIIS-Fundación Jiménez Díaz bREDinREN cUniversidad Autonoma de Madrid dIRSIN, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Ramos
mesh_terms: D000818:Animals; D000074049:Cytokine TWEAK; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D064804:Urological Agents / Q000627:therapeutic use
chemical_list: D000074049:Cytokine TWEAK; D018836:Inflammation Mediators; C109743:TNFSF12 protein, human; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D064804:Urological Agents