» Articles » PMID: 25743111

Long Noncoding RNA Arid2-IR Is a Novel Therapeutic Target for Renal Inflammation

Overview
Journal Mol Ther
Publisher Cell Press
Date 2015 Mar 7
PMID 25743111
Citations 65
Authors
Affiliations
Soon will be listed here.
Abstract

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-β1 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-β-induced Smad3 signaling and fibrosis but inhibited interleukin-1β-stimulated NF-κB-dependent inflammatory response. In contrast, overexpression of Arid2-IR promoted interleukin-1β-induced NF-κB signaling and inflammatory cytokine expression without alteration of TGF-β1-induced fibrotic response. Furthermore, treatment of obstructed kidney with Arid2-IR shRNA blunted NF-κB-driven renal inflammation without effect on TGF-β/Smad3-mediated renal fibrosis. Thus, Arid2-IR is a novel lncRNA that functions to promote NF-κB-dependent renal inflammation. Blockade of Arid2-IR may represent a novel and specific therapy for renal inflammatory disease.

Citing Articles

TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).

Li J, Zou Y, Kantapan J, Su H, Wang L, Dechsupa N Mol Med Rep. 2024; 30(2).

PMID: 38904198 PMC: 11208996. DOI: 10.3892/mmr.2024.13267.


Mechanisms of norcantharidin against renal tubulointerstitial fibrosis.

Yun Q, Bao Y, Jiang J, Guo Q Pharmacol Rep. 2024; 76(2):263-272.

PMID: 38472637 DOI: 10.1007/s43440-024-00578-5.


Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs.

Gu Y, Liu X, Lan H Mol Ther. 2023; 32(2):313-324.

PMID: 38093516 PMC: 10861968. DOI: 10.1016/j.ymthe.2023.12.009.


Insight into Cancer Immunity: MHCs, Immune Cells and Commensal Microbiota.

Wen M, Li Y, Qin X, Qin B, Wang Q Cells. 2023; 12(14).

PMID: 37508545 PMC: 10378520. DOI: 10.3390/cells12141882.


Angiotensin II mediates hypertensive cardiac fibrosis via an Erbb4-IR-dependent mechanism.

Li J, Jia J, Dong L, Hu Z, Huang X, Wang H Mol Ther Nucleic Acids. 2023; 33:180-190.

PMID: 37449045 PMC: 10336735. DOI: 10.1016/j.omtn.2023.06.017.


References
1.
Chung A, Huang X, Zhou L, Heuchel R, Lai K, Lan H . Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice. Nephrol Dial Transplant. 2008; 24(5):1443-54. DOI: 10.1093/ndt/gfn699. View

2.
Park J, Lee M, Cho K, Park B, Chae K, Byun D . Transforming growth factor-beta1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene. 2003; 22(28):4314-32. DOI: 10.1038/sj.onc.1206478. View

3.
Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

4.
Ashcroft G, Yang X, Glick A, Weinstein M, Letterio J, Mizel D . Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol. 1999; 1(5):260-6. DOI: 10.1038/12971. View

5.
Sui W, Li H, Ou M, Tang D, Dai Y . Altered long non-coding RNA expression profile in patients with IgA-negative mesangial proliferative glomerulonephritis. Int J Mol Med. 2012; 30(1):173-8. DOI: 10.3892/ijmm.2012.975. View