title: Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.
abstract: Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. 15991798305@163.com.
authors.forename: Minlong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. wangli344@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, China. dongmqxh@fmmu.edu.cn.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, China. lizhic@fmmu.edu.cn.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. jinfag@fmmu.edu.cn.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D010641:Phenotype; D011015:Pneumonia, Aspiration / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012623:Seawater / Q000009:adverse effects*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; C558466:Sema7a protein, rat; D039961:Semaphorins