title: HSPA12B attenuates acute lung injury during endotoxemia in mice.
abstract: Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat shock protein A12B (HSPA12B), an endothelial cell-expressed heat shock protein, shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts protective effects against ALI during sepsis/septic shock. In this study, we treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for 6h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries as evidenced by microarchitecture destruction, vascular leakage and neutrophil recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were significantly attenuated in Tg mice. Moreover, the LPS-induced activation of extracellular signal-regulated kinases (ERKs) and upregulation of intercellular adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg lungs compared with that in WT mice. Additionally, Tg lungs showed a significant lower level of vascular endothelial growth factor (VEGF) compared with WT mice. Our results demonstrate a pulmonary protective effect of HSPA12B against endotoxin challenge, which indicates management of HSPA12B expression could serve as a potential therapeutic target for ALI during sepsis/septic shock.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, East Tennessee State University, Johnson City TN37614 United States.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing 210029 China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: liuli@njmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; C513783:HSPA12B protein, mouse; D008070:Lipopolysaccharides; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Acute lung injury; Endotoxemia; HSPA12B; Inflammation; Vascular leakage