The Functional Role of Neat1 in Diabetic Kidney Disease

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Background: Long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (Neat1) serves as a key structural component of paraspeckle assembly, which has been implicated in a variety of biological processes. Increased Neat1 expression is associated with inflammatory responses and the pathogenesis of acute kidney injury. Yet, it remains unknown whether Neat1 also regulates inflammatory pathways in chronic kidney disease (CKD), especially in diabetic kidney disease (DKD). Methods: Streptozotocin (STZ)-induced DKD was established in C57B6 mice with a low-dose injection protocol for 5 consecutive days. Neat1 gene was specifically knocked down in the kidney by shRNA gene silencing via ultrasound-mediated microbubble gene transfer. After 10 weeks, all mice were sacrificed for analysis of kidney function, morphology, and expression of inflammatory and fibrotic markers. Results: Neat1 expression was induced in STZ-induced diabetic kidneys. Overexpression of IL-6 and CCL-2 in diabetic mice was attenuated by Neat1 knockdown in which kidney function was preserved with less kidney tubular injury compared to diabetic control mice. Expression of fibrotic markers, such as fibronectin and collagen-1 was decreased in diabetic mice with Neat1 knockdown. Conclusions: Neat1 plays a pathogenetic role in DKD and its knock-down could alleviate diabetic kidney injury. Funding: Research Grants Council of Hong Kong (Collaborative Research Fund, grant no. C7018-16G), and Hong Kong Society of Nephrology/HK Kidney Foundation Research Grant 2019.

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