CCN2 and renal fibrosis: Zhao et al. demonstrated that 14 weeks of high-intensity exercise (60 min/day, five times/week for 14 weeks) activated the transient receptor potential vanilloid 4 (TRPV4)-TGF-β1-Smad2/3-CTGF signaling pathway through elevated lactic acid levels, leading to worsened renal fibrosis [29].