Insulin‐like growth factor 1 knockdown attenuates high glucose‐induced podocyte injury by promoting the JAK2/STAT signalling‐mediated autophagy

Abstract Purpose Podocyte injury plays a crucial role in the development of diabetic nephropathy (DN). A high serum level of insulin‐like growth factor 1 (IGF‐1) has been observed in patients with DN. This paper is to study the role and mechanism of IGF‐1 in high glucose (HG)‐induced podocyte injury. Methods Mouse podocytes MPC‐5 were treated with HG to establish a DN model in vitro. db/db diabetic mice and db/m nondiabetic mice were used to evaluate the IGF‐1 role in vivo. Western blotting was used for measuring protein levels of IGF‐1 receptor, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway‐related markers, podocyte markers podocin and nephrin, apoptosis‐ and autophagy‐related markers in MPC‐5 cells. Immunofluorescence staining was implemented for measuring the expression of nephrin and the autophagy marker LC3. Flow cytometry was used for detecting podocyte apoptosis. Results IGF‐1 expression was increased in HG‐stimulated MPC‐5 cells and the kidney of db/db diabetic mice compared with corresponding controls. Knocking down IGF‐1 downregulated IGF‐1R and inhibited JAK2/STAT signalling pathway in HG‐treated MPC‐5 cells and db/db diabetic mice. IGF‐1 silencing attenuated HG‐induced podocyte injury, apoptosis and reduction in autophagy. Activating the JAK2/STAT signalling pathway or inhibiting autophagy reversed the effects of IGF‐1 silencing on HG‐treated MPC‐5 cells. Conclusion Knocking down IGF‐1 alleviates HG‐induced podocyte injury and apoptosis by inactivating the JAK2/STAT signalling pathway and enhancing autophagy. image