LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy.
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.
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Hong
H
Yi
Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
Rui
R
Peng
Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Lu-Yu
LY
Zhang
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Yan
Y
Sun
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Experimental Teaching Center, Chongqing Medical University, Chongqing, China.
Hui-Min
HM
Peng
Experimental Teaching Center, Chongqing Medical University, Chongqing, China.
Han-Deng
HD
Liu
Experimental Teaching Center, Chongqing Medical University, Chongqing, China.
Li-Juan
LJ
Yu
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Ai-Ling
AL
Li
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Ya-Juan
YJ
Zhang
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Wen-Hao
WH
Jiang
Department of Cell Biology and Medical Genetics, Chongqing Medical University, Chongqing, China.|Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Zheng
Z
Zhang
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D015415:Biomarkers; D016207:Cytokines; D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D062085:RNA, Long Noncoding