Arid2-IR promotes NF-κB-mediated renal inflammation by targeting NLRC5 transcription
| Autor: | Puhua Zhang, Zhijian Li, Hui-Yao Lan, Chaolun Yu, Q.F. Zhou, Jianwen Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Transcription Genetic Inflammation Kidney Filamin Transforming Growth Factor beta1 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Transcription (biology) NLRC5 medicine Animals Humans FLNA Molecular Biology Cells Cultured Mice Knockout Pharmacology 0303 health sciences biology Gene Expression Profiling 030302 biochemistry & molecular biology Intracellular Signaling Peptides and Proteins NF-kappa B NF-κB Cell Biology Transforming growth factor beta Cell biology Mice Inbred C57BL Disease Models Animal HEK293 Cells medicine.anatomical_structure Gene Expression Regulation chemistry biology.protein Molecular Medicine Kidney Diseases RNA Long Noncoding medicine.symptom |
| Zdroj: | Cellular and Molecular Life Sciences. 78:2387-2404 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-020-03659-9 |
| Popis: | Increasing evidence shows that long non-coding RNAs (lncRNAs) play an important role in a variety of disorders including kidney diseases. It is well recognized that inflammation is the initial step of kidney injury and is largely mediated by nuclear factor Kappa B (NF-κB) signaling. We had previously identified lncRNA-Arid2-IR is an inflammatory lncRNA associated with NF-κB-mediated renal injury. In this study, we examined the regulatory mechanism through which Arid2-IR activates NF-κB signaling. We found that Arid2-IR was differentially expressed in response to various kidney injuries and was induced by transforming growth factor beta 1(TGF-β1). Using RNA sequencing and luciferase assays, we found that Arid2-IR regulated the activity of NF-κB signal via NLRC5-dependent mechanism. Arid2-IR masked the promoter motifs of NLRC5 to inhibit its transcription. In addition, during inflammatory response, Filamin A (Flna) was increased and functioned to trap Arid2-IR in cytoplasm, thereby preventing its nuclear translocation and inhibition of NLRC5 transcription. Thus, lncRNA Arid2-IR mediates NF-κB-driven renal inflammation via a NLRC5-dependent mechanism and targeting Arid2-IR may be a novel therapeutic strategy for inflammatory diseases in general. |
| Databáze: | OpenAIRE |
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