C1q/Tumor Necrosis Factor-Related Protein-9 Attenuates Diabetic Nephropathy and Kidney Fibrosis in db/db Mice.

Diabetic nephropathy (DN) is characterized by excessive accumulation of extracellular matrix leading to early thickening of glomerular and tubular basement membrane. C1q/tumor necrosis factor (TNF)-related protein-9 (CTRP9) was recently identified as an adiponectin paralog of superior prominence. CTRP9 is an anti-inflammatory, antioxidant, vasodilation and atheroprotective adipose cytokine that share a similar metabolic regulatory function as adiponectin. Additionally, CTRP9 inhibits apoptosis of endothelial cells, decreases blood glucose level, and increases insulin sensitivity. However, the renoprotective effects of CTRP9 and the underlying molecular mechanisms in DN have not been explored. This study examined the effects of CTRP9 on DN in diabetic db/db mice through adenovirus-mediated overexpression. From the results, CTRP9 ameliorated renal dysfunction and injury at the structural and functional level in diabetic db/db mice. Additionally, CTRP9 inhibited glomerular and tubular glycogen accumulation, fibrosis, relieved hyperglycemia-mediated oxidative stress, and apoptosis. This is the first study to report on therapeutic effects of CTRP9 on DN, presenting a potentially effective clinical treatment method for DN patients.