Identification of novel long noncoding RNAs associated with TGF-β/Smad3-mediated renal inflammation and fibrosis by RNA sequencing.

Abstract

We have previously shown that transforming growth factor-β/Smad3-dependent miRNAs play a critical role in renal inflammation and fibrosis. However, off-target effects of miRNAs limit their therapeutic application. Recently, emerging roles of long noncoding RNAs (lncRNAs) in diseases have been recognized. In this study, we used high-throughput RNA sequencing to identify the Smad3-dependent lncRNAs related to renal inflammation and fibrosis in Smad3 knockout mouse models of unilateral ureteral obstructive nephropathy and immunologically induced anti-glomerular basement membrane glomerulonephritis. 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 lncRNAs were up-regulated in wild-type, 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. Real-time 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.

• Authors: Qin Zhou, Arthur C K Chung, Xiao R Huang, Yuan Dong, Xueqing Yu, Hui Y Lan
• Journal: The American journal of pathology (Am J Pathol) Vol. 184 Issue 2 Pg. 409-17 (Feb 2014) ISSN: 1525-2191 [Electronic] United States
• PMID: 24262754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• RNA, Long Noncoding
• Smad3 Protein
• Transforming Growth Factor beta

Topics

• Animals
• Base Sequence
• Binding Sites
• Female
• Fibrosis
• Gene Expression Regulation
• Gene Ontology
• Glomerulonephritis (genetics, pathology)
• Inflammation (genetics, pathology)
• Kidney (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• Protein Binding
• RNA, Long Noncoding (genetics, metabolism)
• Sequence Analysis, RNA
• Signal Transduction
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta (metabolism)
• Ureteral Obstruction (genetics, pathology)