MicroRNA‐223 alleviates inflammatory response in renal ischemia‐reperfusion injury by targeting NLRP3

Autor: Jun Ye, Xiaoli Tang, Ming Li, Yutian Liao, Yiqian Zeng, Furong Tang, Eryue Qiu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Kaohsiung Journal of Medical Sciences, Vol 40, Iss 9, Pp 789-800 (2024)
Druh dokumentu: article
ISSN: 2410-8650
1607-551X
DOI: 10.1002/kjm2.12883
Popis: Abstract We investigated the potential correlation between miR‐223 and NAcHT, LRR, and PYd domain‐containing protein 3 (NLRP3) in the context of renal ischemia‐reperfusion injury (RIRI), which is a leading cause of acute renal failure with significant mortality rates. Additionally, miR‐223 has been implicated in renal inflammation, further highlighting its relevance to this study. C57BL/6 male mice were used as RIRI models. After successful modeling, pathological examinations and serum creatinine and miR‐223 levels were tested. Pro‐inflammatory cytokine (IL‐1β, IL‐6, IL‐8, NLPR3, TLR4) expression was detected in mice by western blot (kidney tissue) and enzyme‐linked immunosorbent assay (serum). HK‐2 cells were used for in vitro experiments. A hypoxia/reoxygenation (H/R) model was used, and miR‐223 and pro‐inflammatory cytokine levels were detected using PCR and western blot assays, respectively. A dual‐luciferase reporter assay was conducted to confirm the binding of miR‐223 to NLPR3. Next, NLRP3 was knocked down to determine whether the anti‐inflammatory function of miR‐223 is dependent on NLRP3. MiR‐223 expression was lower in RIRI mice than in the sham operation group. The level of miR‐223 negatively correlated with serum creatinine levels and the severity of tubule injury. Increased proinflammatory cytokine levels in RIRI mice were observed. In vitro, miR‐223 alleviated the inflammatory response in H/R treated cells by inhibiting proinflammatory cytokines. Dual‐luciferase reporter and western blot assays confirmed the binding of miR‐223 to NLRP3. NLRP3 knockdown reversed the anti‐inflammatory effects of miR‐223 in HK‐2 cells. MiR‐223 plays an anti‐inflammatory role in RIRI by targeting NLRP3 to repress pro‐inflammatory factors.
Databáze: Directory of Open Access Journals
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