Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) in kidney disease: a biomarker or therapeutic target?

Abstract

Kidney disease is a significant public health problem that is increasing worldwide. Tumour necrosis factor superfamily molecules have recently been shown to be actively involved in renal pathophysiology. According to current reports, one of these molecules has significant clinical implications: TWEAK, a tumour necrosis factor-like weak inducer of apoptosis. TWEAK is a cytokine with important functions. By binding to induced fibroblast growth factor 14 (Fn14), its only receptor, TWEAK activates various biological processes, including cell growth, migration or death, angiogenesis and production of proinflammatory cytokines. TWEAK and Fn14 expression is relatively low in healthy tissues. Experimental studies have confirmed the important role of TWEAK/Fn14 pathway activation in physiological tissue repair and regeneration, while its excessive activation leads to acute and/or chronic damage. TWEAK production takes place in various inflammatory diseases of the kidneys with the participation of immune cells. In the case of inflammatory diseases characterised by increased chemokine production, TWEAK presents with apoptotic effects. In non-immune diseases, TWEAK stimulates renal tubular proliferation. The dualism of the TWEAK effect is multifactorial. TWEAK was proliferative in healthy kidneys and in a compensatory overgrowth model after nephrectomy in which inflammatory cytokine expression was low. Data obtained from experimental and clinical studies are useful for developing future diagnostic and therapeutic strategies focused on the role of TWEAK in kidney damage.