A Novel Role of Adipokine 'Intelectin-1': Ameliorating Renal Fibrosis Through Inhibition of Renal Tubular Epithelial Cell Senescence.

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.