PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway.

Abstract

To investigate whether Plasmacytoma Variant Translocation 1 (PVT1) could regulate the occurrence and progression of diabetic peripheral neuropathy (DPN) via activating the PI3K/AKT pathway. Diabetes model in rats was constructed by streptozotocin (STZ) injection. PVT1 expression in diabetic rats and control rats was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Rats were injected with PVT1 overexpression lentivirus or vector, respectively, followed by determination of mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL) and sensory nerve conduction velocity (SNCV). Cell apoptosis of dorsal root ganglia (DRG) was accessed by TUNEL. Western blot was performed to detect the expressions of neurodegeneration-related genes and neurogenesis-related genes. The regulatory effect of PVT1 on the PI3K/AKT pathway was detected by Western blot. PVT1 was downregulated in diabetic rats compared with that of controls. Diabetic rats presented higher MWT, TWL and SNCV. Cell apoptosis of DRG was pronounced in diabetic rats. The amount of inflammation-related glial cells increased in diabetic rats. PVT1 overexpression remarkably decreased MWT and TWL. PVT1 downregulated expressions of neurodegeneration-related genes and upregulated neurogenesis-related genes. Western blot results suggested that PI3K/AKT pathway in diabetic rats was blocked, which was reversed by PVT1 overexpression. PVT1 is lowly expressed in diabetic rats, leading to decreased mechanical withdrawal threshold, thermal withdrawal latency and sensory nerve conduction velocity. PVT1 protects diabetic peripheral neuropathy via PI3K/AKT pathway.