FC 119: Kidney-Specific Silencing of Neat1 Alleviates Diabetic Kidney Injury

Abstract

Abstract BACKGROUND AND AIMS Long noncoding RNA Nuclear Enriched Abundant Transcript 1 (Neat1) not only serves as a key structural component of nuclear paraspeckle, but is also involved in a variety of pathophysiological processes. Our previous study shows that increased Neat1 expression is closely associated with the pathogenesis of acute kidney injury. Here, we investigate whether Neat1 plays a role in chronic kidney disease and diabetes (DKD). METHOD Neat1 expression on kidney biopsies of patients with DKD and other nondiabetic kidney disease was measured by in situ hybridization. Normal portions of kidney tissues removed from nephrectomy specimens for the treatment of renal carcinoma was used as control. In vivo, streptozotocin (STZ)-induced DKD was established in uninephrectomized C57BL/6 mice with low-dose STZ (50 mg/kg) injection for five consecutive days. Mice injected with citrate buffer were used as control. Neat 1 gene was subsequently knocked down in the kidney by shRNA gene silencing via ultrasound-mediated microbubble technique every 2 weeks. All mice were sacrificed at 10 weeks after STZ injection for renal histopathological examination, urine albumin-to-creatinine ratio (UACR) measurement and Neat 1 expression analysis. RESULTS Kidney Neat 1 expression was increased significantly in DKD patients compared with control and other kidney diseases (Figure 1). Similarly, Neat1 was induced in STZ-induced diabetic kidneys while its expression was markedly suppressed following shRNA knockdown as confirmed by real-time qPCR (Figure 2A, C and E). Compared with nondiabetic control, diabetic mice presented increased UACR with significant tubular dilatation and atrophy, while knockdown of Neat1 attenuated both proteinuria and kidney injury in the diabetic mice (Figure 2B, D and F). CONCLUSION Increased Neat 1 expression contributes to the pathogenesis of DKD and targeting Neat 1 may be a novel and potential therapeutic strategy for diabetic kidney injury.