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

Am J Pathol. 2014 Feb;184(2):409-17. doi: 10.1016/j.ajpath.2013.10.007. Epub 2013 Nov 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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