The American journal of pathology, 2014-02, Vol.184 (2), p.409-417
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Identification of Novel Long Noncoding RNAs Associated with TGF-β/Smad3-Mediated Renal Inflammation and Fibrosis by RNA Sequencing
- Ist Teil von
- The American journal of pathology, 2014-02, Vol.184 (2), p.409-417
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0002-9440eISSN: 1525-2191DOI: 10.1016/j.ajpath.2013.10.007Titel-ID: cdi_proquest_miscellaneous_1490762309
- Format
- –
- Schlagworte
- 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, Pathology, 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