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The epigenetic regulator BRD4 is involved in cadmium-triggered inflammatory response in rat kidney.
- Source :
-
Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2021 Aug 13; Vol. 224, pp. 112620. Date of Electronic Publication: 2021 Aug 13. - Publication Year :
- 2021
- Publisher :
- Ahead of Print
-
Abstract
- Cadmium (Cd) has been described as a potential inflammatory inducer, while increasing evidence shows that inappropriate inflammation is a contributing factor to kidney injury. Hence, research on Cd-triggered inflammatory response is of great significance for elucidating the mechanism of Cd-induced nephrotoxicity. Bromodomain-containing 4 (BRD4) is an important epigenetic regulator involved in the development of many inflammatory diseases, but its regulatory roles in Cd-triggered inflammatory response remain to be clarified. Here, we found that treatment with Cd in Sprague-Dawley rats (2 mg/kg bw, i.p., 5 consecutive days) and in rat kidney cell line (NRK-52E, 0-10 μM, 12 h) induced the transcription of inflammatory cytokines, which could be reduced by JQ1 (BRD4 inhibitor, 25 mg/kg bw, i.p., 3 consecutive days in vivo; 0.5 μM, 12 h in vitro) or BRD4 small interfering RNA (siRNA, in vitro), suggesting that BRD4 participates in Cd-triggered inflammatory response. Next, our study clarified the roles of BRD4 in Cd-triggered inflammatory response. The inhibition of BRD4 decreased Cd-promoted NF-κB nuclear translocation and activation in vivo and in vitro. Cd increased the acetylation level of RelA K310 and enhanced BRD4 binding to acetylated NF-κB RelA in vivo and in vitro, which were abrogated by inhibiting BRD4. In summary, our study suggests that BRD4 is involved in Cd-triggered transcription of inflammatory cytokines by mediating the activation of NF-κB signaling pathway and increasing itself binding to acetylated NF-κB RelA in rat kidney, therefore, BRD4 could be a potential therapeutic target for Cd-induced renal diseases.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1090-2414
- Volume :
- 224
- Database :
- MEDLINE
- Journal :
- Ecotoxicology and environmental safety
- Publication Type :
- Academic Journal
- Accession number :
- 34392152
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2021.112620