title: 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.affiliation: Department of Medicine and Therapeutics, the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Medicine and Therapeutics, the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Arthur C K
authors.initials: AC
authors.lastname: Chung
authors.affiliation: Department of Medicine and Therapeutics, the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xiao R
authors.initials: XR
authors.lastname: Huang
authors.affiliation: Department of Medicine and Therapeutics, the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: yuxq@mail.sysu.edu.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Medicine and Therapeutics, the Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China. Electronic address: hylan@cuhk.edu.hk.
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Lan
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D063990:Gene Ontology; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000235:genetics / Q000473:pathology
chemical_list: D062085:RNA, Long Noncoding; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta