Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in Diabetic Nephropathy

Zhang, Nanwen; Zheng, Qingmei; Wang, Yaduan; Lin, Juan; Wang, He; Liu, Rui; Yan, Mengru; Chen, Xiaofeng; Yang, Juhua; Chen, Xiaole

Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a dual target-directed single domain-based fusion protein against the interleukin-6 receptor. This study aims to explore the renoprotective effect of VHH-0031 in diabetic nephropathy. VHH-0031 treatment alleviated renal inflammation, morphologic injury and renal insufficiency in both Goto-Kakizaki rats and STZ-induced Sprague Dawley rats. These renoprotective effects of VHH-0031 are associated with alleviating inflammation and suppression of the JAK2/STAT3 signaling pathway. The mesangial cells treated with VHH-0031 exhibited anti-proliferation, anti-inflammation and inactivation of JAK2/STAT3 pathway under high glucose condition. In conclusion, this study demonstrates that VHH-0031 exhibited a potent protective effect in kidney of diabetic rats and its mechanism may be concerned with the inhibition of the IL-6R/JAK2/STAT3 pathway of glomerular mesangial cells.