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LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy.
Cell Death Dis. 2017 02 02; 8(2):e2583.CD

Abstract

Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown. Our previous study has revealed that 14 lncRNAs are abnormally expressed in DN by RNA sequencing and real-time quantitative PCR (qRT-PCR) in the renal tissues of db/db DN mice. In this study, these lncRNAs were verified their expressions by qRT-PCR in mesangial cells (MCs) cultured under high- and low-glucose conditions. Twelve lncRNAs displayed the same expressional tendencies in both renal tissues and MCs. In particular, long intergenic noncoding RNA (lincRNA)-Gm4419 was the only one associating with NF-κB among these 12 lncRNAs by bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit the expressions of pro-inflammatory cytokines and renal fibrosis biomarkers, and reduce cell proliferation in MCs under high-glucose condition, whereas overexpression of Gm4419 could increase the inflammation, fibrosis and cell proliferation in MCs under low-glucose condition. Interestingly, our results showed that Gm4419 could activate the NF-κB pathway by directly interacting with p50, the subunit of NF-κB. In addition, we found that p50 could interact with NLRP3 inflammasome in MCs. In conclusion, our findings suggest lincRNA-Gm4419 may participate in the inflammation, fibrosis and proliferation in MCs under high-glucose condition through NF-κB/NLRP3 inflammasome signaling pathway, and may provide new insights into the regulation of Gm4419 during the progression of DN.

Authors+Show Affiliations

Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Bioinformatics, Chongqing Medical University, Chongqing, China.Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Experimental Teaching Center, Chongqing Medical University, Chongqing, China.Experimental Teaching Center, Chongqing Medical University, Chongqing, China.Experimental Teaching Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28151474

Citation

Yi, Hong, et al. "LincRNA-Gm4419 Knockdown Ameliorates NF-κB/NLRP3 Inflammasome-mediated Inflammation in Diabetic Nephropathy." Cell Death & Disease, vol. 8, no. 2, 2017, pp. e2583.
Yi H, Peng R, Zhang LY, et al. LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. Cell Death Dis. 2017;8(2):e2583.
Yi, H., Peng, R., Zhang, L. Y., Sun, Y., Peng, H. M., Liu, H. D., Yu, L. J., Li, A. L., Zhang, Y. J., Jiang, W. H., & Zhang, Z. (2017). LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. Cell Death & Disease, 8(2), e2583. https://doi.org/10.1038/cddis.2016.451
Yi H, et al. LincRNA-Gm4419 Knockdown Ameliorates NF-κB/NLRP3 Inflammasome-mediated Inflammation in Diabetic Nephropathy. Cell Death Dis. 2017 02 2;8(2):e2583. PubMed PMID: 28151474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. AU - Yi,Hong, AU - Peng,Rui, AU - Zhang,Lu-Yu, AU - Sun,Yan, AU - Peng,Hui-Min, AU - Liu,Han-Deng, AU - Yu,Li-Juan, AU - Li,Ai-Ling, AU - Zhang,Ya-Juan, AU - Jiang,Wen-Hao, AU - Zhang,Zheng, Y1 - 2017/02/02/ PY - 2016/08/28/received PY - 2016/11/14/revised PY - 2016/11/28/accepted PY - 2017/2/3/entrez PY - 2017/2/6/pubmed PY - 2017/10/28/medline SP - e2583 EP - e2583 JF - Cell death & disease JO - Cell Death Dis VL - 8 IS - 2 N2 - Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown. Our previous study has revealed that 14 lncRNAs are abnormally expressed in DN by RNA sequencing and real-time quantitative PCR (qRT-PCR) in the renal tissues of db/db DN mice. In this study, these lncRNAs were verified their expressions by qRT-PCR in mesangial cells (MCs) cultured under high- and low-glucose conditions. Twelve lncRNAs displayed the same expressional tendencies in both renal tissues and MCs. In particular, long intergenic noncoding RNA (lincRNA)-Gm4419 was the only one associating with NF-κB among these 12 lncRNAs by bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit the expressions of pro-inflammatory cytokines and renal fibrosis biomarkers, and reduce cell proliferation in MCs under high-glucose condition, whereas overexpression of Gm4419 could increase the inflammation, fibrosis and cell proliferation in MCs under low-glucose condition. Interestingly, our results showed that Gm4419 could activate the NF-κB pathway by directly interacting with p50, the subunit of NF-κB. In addition, we found that p50 could interact with NLRP3 inflammasome in MCs. In conclusion, our findings suggest lincRNA-Gm4419 may participate in the inflammation, fibrosis and proliferation in MCs under high-glucose condition through NF-κB/NLRP3 inflammasome signaling pathway, and may provide new insights into the regulation of Gm4419 during the progression of DN. SN - 2041-4889 UR - https://www.unboundmedicine.com/medline/citation/28151474/LincRNA_Gm4419_knockdown_ameliorates_NF_κB/NLRP3_inflammasome_mediated_inflammation_in_diabetic_nephropathy_ L2 - https://doi.org/10.1038/cddis.2016.451 DB - PRIME DP - Unbound Medicine ER -