American Journal of Physiology - Endocrinology and Metabolism
American Journal of Physiology - Endocrinology and Metabolism
5 years ago

ANRIL regulates production of extracellular matrix proteins and vasoactive factors in Diabetic Complications.

Subrata Chakrabarti, Biao Feng, Anu Alice Thomas
Long non-coding RNAs (lncRNAs) have gained widespread interest due to their prevailing presence in various diseases. lncRNA ANRIL (a.k.a CDKN2B-AS1) is located on human chromosome 9 (p21.3) and transcribed in opposite direction to INK4b-ARF-INK4a gene cluster. It has been identified as highly susceptible region for diseases such as coronary artery diseases and Type 2 Diabetes. Here we explored its regulatory role in diabetic nephropathy (DN) and diabetic cardiomyopathy (DCM) in association with epigenetic modifiers p300 and polycomb repressive complex 2 (PRC2) complex. We used an ANRIL knockout (ANRILKO) mouse model for this study. The wildtype and ANRILKO animals with or without streptozotocin-induced diabetes were monitored for 2m. At the end of the timepoint, urine and tissues were collected. The tissues were measured for fibronectin (FN), type IV collagen (Col1α4) and VEGF mRNA and protein expressions. Renal function was determined by the measurement of 24h urine volume and Albumin/Creatinine ratio at sacrifice. Renal and cardiac structures were investigated using periodic acid-Schiff stain and/or immunohistochemical analysis. Elevated expressions of extracellular matrix (ECM) proteins, were prevented in ANRILKO diabetic animals. Furthermore, ANRILKO had a protective effect on the diabetic mouse kidneys as evidenced by lowering of urine volume and urine albumin levels in comparison to the wildtype diabetics. These alterations regulated by ANRIL were mediated by p300 and enhancer of zeste 2 (EZH2) of the PRC2 complex. Our study concludes that ANRIL regulates functional and structural alterations in the kidneys and hearts in diabetes through controlling the expressions of ECM proteins and VEGF.

Publisher URL: http://doi.org/10.1152/ajpendo.00268.2017

DOI: 10.1152/ajpendo.00268.2017

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