期刊
MOLECULAR THERAPY
卷 23, 期 6, 页码 1034-1043出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2015.31
关键词
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资金
- Major State Basic Research Development Program of China [2012CB5177005]
- National Natural Science Foundation of China [81130012]
- National Natural Science Foundation [81100542, 81470942]
- Research Grant Council of Hong Kong [GRF 468711, CUHK3/CRF/12R, TRS T12-402/13N]
- Focused Investment Scheme A program from the Chinese University of Hong Kong
Increasing evidence shows that microRNAs play an important role in kidney disease. However, functions of long noncoding RNAs (lncRNAs) in kidney diseases remain undefined. We have previously shown that TGF-beta 1 plays a diverse role in renal inflammation and fibrosis and Smad3 is a key mediator in this process. In this study, we used RNA-sequencing to identify lncRNAs related to renal inflammation and fibrosis in obstructive nephropathy induced in Smad3 wild-type and knockout mice. We found that Arid2-IR was a Smad3-associated lncRNA as a Smad3 binding site was found in the promoter region of Arid2-IR and deletion of Smad3 abolished upregulation of Arid2-IR in the diseased kidney. In vitro knockdown of Arid2-IR from tubular epithelial cells produced no effect on TGF-beta-induced Smad3 signaling and fibrosis but inhibited interleukin-1 beta-stimulated NF-kappa B-dependent inflammatory response. In contrast, overexpression of Arid2-IR promoted -interleukin-1 beta-induced NF-kappa B signaling and inflammatory cytokine expression without alteration of TGF-beta 1-induced fibrotic response. Furthermore, treatment of obstructed kidney with Arid2-IR shRNA blunted NF-kappa B-driven renal inflammation without effect on TGF-beta/Smad3-mediated renal fibrosis. Thus, Arid2-IR is a novel lncRNA that functions to promote NF-kappa B-dependent renal inflammation. Blockade of Arid2-IR may represent a novel and specific therapy for renal inflammatory disease.
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