Inhibitor of IGF1 receptor alleviates the inflammation process in the diabetic kidney mouse model without activating SOCS2

• Main Authors: Li J, Dong R, Yu J, Yi S, Da J, Yu F, Zha Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-09-01
• Series: Drug Design, Development and Therapy
• Subjects: Diabetes kidney disease; IGF-1R inhibitor; insulin; SOCS2
• Online Access: https://www.dovepress.com/inhibitor-of-igf1-receptor-alleviates-the-inflammation-process-in-the--peer-reviewed-article-DDDT

Jiayu Li,1 Rong Dong,2 Jiali Yu,2 Sun Yi,2 Jingjing Da,2 Fuxun Yu,3 Yan Zha2 1Guizhou University School of Medicine, Guizhou University, 2Department of Nephrology, Guizhou Provincial People’s Hospital, 3Department of Central Laboratory, Guizhou Provincial People’s Hospital, Guiyang, China Objective: To explore the anti-inflammatory mechanism of IGF1R inhibitor in diabetic nephropathy.Methods: C57/BL6 mice were reared with high-fat diet for 8 weeks, then were injected 30 mg/kg streptozotocin intraperitoneally to induce type 2 diabetes. After 8 weeks, the type 2 diabetes nephropathy model was successfully set up the different drugs were administrated to mice with diabetes (insulin 1–2 U/day, benazepril 10 mg/kg per day intragastrically, IGF-1R inhibitor 30 mg/kg per day intragastrically). After 8 weeks drugs administration, all mice were collected the kidney tissue, measured levels of inflammatory factor (F4/80, TLR4and CD68) and fibrosis markers(αSMA, E-cadherin and SR) using immunohistochemistry and in situ hybridization.Results: The type 2 diabetes nephropathy model was built successfully, which along with increased urinary protein excretion rate and increased inflammatory infiltration, and the correlation was characterized by increased CD68+, F4/80+ cells and increased TLR4, αSMA, SR expression. IGF-1R inhibitors reversed this changes, but benazepril and insulin were without significant changes. The insulin decreased the expression level of IGF-1, and increased the levels of suppressor of cytokine signaling 2 (SOCS2). Benazepril and IGF-1R inhibitor were no significant changes like insulin.Conclusion: Inhibition of IGF1R was a more effective choice for inflammation treatment than Ben or Ins in diabetic kidney disease (DKD). The IGF1R inhibitor blocked pathological changes induced by the over-expression of IGF1 in DKD without up-regulating SOCS2 protein levels. Keywords: diabetes kidney disease, IGF1R inhibitor, insulin, SOCS2