A Novel Role of Adipokine ‘Intelectin‐1’: Ameliorating Renal Fibrosis Through Inhibition of Renal Tubular Epithelial Cell Senescence

ABSTRACT Renal fibrosis is a common pathological process associated with chronic kidney disease (CKD) progression. Intelectin‐1, a newly identified adipokine, has been demonstrated to protect renal function in mice with type 2 diabetic nephropathy. However, the role of intelectin‐1 in renal fibrosis and the underlying mechanisms remain unclear. This study aimed to: (1) investigate the effects of intelectin‐1 on renal fibrosis in mice, and (2) explore the potential involvement of intelectin‐1 in regulating renal tubular epithelial cells (TECs) senescence and mitochondrial dysfunction. To our knowledge, these findings represent the first demonstration that intelectin‐1 treatment significantly attenuates renal fibrosis in unilateral ureteral obstruction (UUO) in mice by effectively inhibiting TECs senescence. Furthermore, intelectin‐1 treatment alleviated mitochondrial dysfunction in TECs, as evidenced by improved mitochondrial membrane potential and decreased mitochondrial reactive oxygen species (mtROS) production. Mechanistically, intelectin‐1 treatment activated AMPK signaling that subsequently inhibited the mTOR and p38 pathways. In conclusion, our findings suggest that intelectin‐1 attenuates renal fibrosis in mice by inhibiting TECs senescence and alleviating mitochondrial dysfunction via AMPK/mTOR/p38MAPK signaling. These results provide a potential therapeutic target for the treatment of renal fibrosis in CKD. Further studies are warranted to explore the clinical relevance and translational potential of adipokines, including intelectin‐1, in human renal fibrosis.