Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway

Abstract Background Tracheal injury is a common clinical condition that still lacks an effective therapy at present. Stimulation of epithelial sodium channel (ENaC) increases Na+ transport, which is a driving force to keep tracheal mucosa free edema fluid during tracheal injury. Ferulic acid (FA) ha...

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Autores principales:	Xiaoyong Xie, Tong Yu, Yapeng Hou, Aixin Han, Yan Ding, Hongguang Nie, Yong Cui
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ferulic acid Tracheal injury Epithelial sodium channel cGMP/PKGII signaling pathway Diseases of the respiratory system RC705-779
Acceso en línea:	https://doaj.org/article/ede9583247eb480c88fbe2a61eb3e962
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spelling	oai:doaj.org-article:ede9583247eb480c88fbe2a61eb3e9622021-12-05T12:20:24ZFerulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway10.1186/s12931-021-01897-41465-993Xhttps://doaj.org/article/ede9583247eb480c88fbe2a61eb3e9622021-12-01T00:00:00Zhttps://doi.org/10.1186/s12931-021-01897-4https://doaj.org/toc/1465-993XAbstract Background Tracheal injury is a common clinical condition that still lacks an effective therapy at present. Stimulation of epithelial sodium channel (ENaC) increases Na+ transport, which is a driving force to keep tracheal mucosa free edema fluid during tracheal injury. Ferulic acid (FA) has been proved to be effective in many respiratory diseases through exerting anti-oxidant, anti-inflammatory, and anti-thrombotic effects. However, these studies rarely involve the level of ion transport, especially ENaC. Methods C57BL/J male mice were treated intraperitoneally with normal saline or FA (100 mg/kg) 12 h before, and 12 h after intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg), respectively. The effects of FA on tracheal injury were not only assessed through HE staining, immunofluorescence assay, and protein/mRNA expressions of ENaC located on tracheas, but also evaluated by the function of ENaC in mouse tracheal epithelial cells (MTECs). Besides, to explore the detailed mechanism about FA involved in LPS-induced tracheal injury, the content of cyclic guanosine monophosphate (cGMP) was measured, and Rp-cGMP (cGMP inhibitor) or cGMP-dependent protein kinase II (PKGII)-siRNA (siPKGII) were applied in primary MTECs, respectively. Results Histological examination results demonstrated that tracheal injury was obviously attenuated by pretreatment of FA. Meanwhile, FA could reverse LPS-induced reduction of both protein/mRNA expressions and ENaC activity. ELISA assay verified cGMP content was increased by FA, and administration of Rp-cGMP or transfection of siPKGII could reverse the FA up-regulated ENaC protein expression in MTECs. Conclusions Ferulic acid can attenuate LPS-induced tracheal injury through up-regulation of ENaC at least partially via the cGMP/PKGII pathway, which may provide a promising new direction for preventive and therapeutic strategy in tracheal injury.Xiaoyong XieTong YuYapeng HouAixin HanYan DingHongguang NieYong CuiBMCarticleFerulic acidTracheal injuryEpithelial sodium channelcGMP/PKGII signaling pathwayDiseases of the respiratory systemRC705-779ENRespiratory Research, Vol 22, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ferulic acid Tracheal injury Epithelial sodium channel cGMP/PKGII signaling pathway Diseases of the respiratory system RC705-779
spellingShingle	Ferulic acid Tracheal injury Epithelial sodium channel cGMP/PKGII signaling pathway Diseases of the respiratory system RC705-779 Xiaoyong Xie Tong Yu Yapeng Hou Aixin Han Yan Ding Hongguang Nie Yong Cui Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
description	Abstract Background Tracheal injury is a common clinical condition that still lacks an effective therapy at present. Stimulation of epithelial sodium channel (ENaC) increases Na+ transport, which is a driving force to keep tracheal mucosa free edema fluid during tracheal injury. Ferulic acid (FA) has been proved to be effective in many respiratory diseases through exerting anti-oxidant, anti-inflammatory, and anti-thrombotic effects. However, these studies rarely involve the level of ion transport, especially ENaC. Methods C57BL/J male mice were treated intraperitoneally with normal saline or FA (100 mg/kg) 12 h before, and 12 h after intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg), respectively. The effects of FA on tracheal injury were not only assessed through HE staining, immunofluorescence assay, and protein/mRNA expressions of ENaC located on tracheas, but also evaluated by the function of ENaC in mouse tracheal epithelial cells (MTECs). Besides, to explore the detailed mechanism about FA involved in LPS-induced tracheal injury, the content of cyclic guanosine monophosphate (cGMP) was measured, and Rp-cGMP (cGMP inhibitor) or cGMP-dependent protein kinase II (PKGII)-siRNA (siPKGII) were applied in primary MTECs, respectively. Results Histological examination results demonstrated that tracheal injury was obviously attenuated by pretreatment of FA. Meanwhile, FA could reverse LPS-induced reduction of both protein/mRNA expressions and ENaC activity. ELISA assay verified cGMP content was increased by FA, and administration of Rp-cGMP or transfection of siPKGII could reverse the FA up-regulated ENaC protein expression in MTECs. Conclusions Ferulic acid can attenuate LPS-induced tracheal injury through up-regulation of ENaC at least partially via the cGMP/PKGII pathway, which may provide a promising new direction for preventive and therapeutic strategy in tracheal injury.
format	article
author	Xiaoyong Xie Tong Yu Yapeng Hou Aixin Han Yan Ding Hongguang Nie Yong Cui
author_facet	Xiaoyong Xie Tong Yu Yapeng Hou Aixin Han Yan Ding Hongguang Nie Yong Cui
author_sort	Xiaoyong Xie
title	Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
title_short	Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
title_full	Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
title_fullStr	Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
title_full_unstemmed	Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway
title_sort	ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cgmp/pkgii signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ede9583247eb480c88fbe2a61eb3e962
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_version_	1718372051040862208

Ferulic acid ameliorates lipopolysaccharide-induced tracheal injury via cGMP/PKGII signaling pathway

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