Urolithin A alleviates respiratory syncytial virus-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling
10.12122/j.issn.1673-4254.2024.07.17
- VernacularTitle:尿石素A通过活化miR-136介导的Sirt1信号通路减轻呼吸道合胞病毒诱导的新生小鼠肺部感染
- Author:
Hongzhe WANG
1
;
Haitang XIE
;
Wulan XU
;
Ming LI
Author Information
1. 内蒙古民族大学附属医院儿科,内蒙古 通辽 028000
- Keywords:
urolithin A;
respiratory syncytial virus;
miR-136;
Sirt1
- From:
Journal of Southern Medical University
2024;44(7):1370-1381
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.
