Identification of Novel Long Noncoding RNAs Associated with TGF-β/Smad3-Mediated Renal Inflammation and Fibrosis by RNA Sequencing

We have previously shown that transforming growth factor-beta/Smad3-dependent miRNAs play a critical role in renal inflammation and fibrosis. However, off-target effects of miRNAs limit their therapeutic application. Recently, emerging rotes of Long noncoding RNAs (lncRNAs) in diseases have been recognized. In this study, we used high-throughput RNA sequencing to identify the Smad3-dependent IncRNAs related to renal inflammation and fibrosis in Smad3 knockout mouse models of unilateral ureteral obstructive nephropathy and immunologically induced anti-glomerular basement membrane gtomerulonephritis. Compared with wild-type mice, 151 lncRNAs in the unilateral ureteral obstructive nephropathy kidney and 413 lncRNAs in kidneys with anti-glomerular basement membrane glomerulonephritis were significantly altered in Smad3 knockout mice. Among them, 21 common IncRNAs were up-regulated in wildtype, but down-regulated in Smad3 knockout, kidneys in both disease models in which progressive renal inflammation and fibrosis were abolished when the Smad3 gene was deleted or suppressed. Realtime PCR confirmed these findings and revealed the functional link between Smad3-dependent lncRNAs np_5318/np_17856 and progressive kidney injury. Results demonstrate that the identification and characterization of functional lncRNAs associated with kidney disease may represent a promising research direction into renal disorder and may lead to the development of new lncRNA therapies for kidney diseases.