Blocking interleukin-6 trans-signaling protects against renal fibrosis by suppressing STAT3 activation
Rationale: Renal fibrosis is the terminal manifestation of chronic and irreversible renal disease. Effective therapies other than dialysis are extremely limited. In this study, we investigated the potential effects of targeting elevated interleukin-6 (IL-6) levels in the treatment of renal fibrosis. Methods: Fc-gp130 was used to specifically block IL-6 trans-signaling. Unilateral ureteral occlusion (UUO) and ischemia reperfusion (IR) mouse models were constructed to investigate the therapeutic effect of Fc-gp130 on renal fibrosis. The role of IL-6 trans-signaling and phosphorylation of signal transducer and activator of transcription (STAT) 3 in regulating fibroblast accumulation and extracellular matrix protein deposition were evaluated in cell experiments and mouse models.