title: Rac1 mediates HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells via MAPK signal transduction.
abstract: The pathology of acute respiratory distress syndrome (ARDS) is closely associated with the failure of alveolar‑capillary barrier integrity and alveolar filling by high protein pulmonary edema, resulting from hyperpermeability. High mobility group box 1 (HMGB1) is a novel late mediator of sepsis, which is specifically involved in endotoxin‑induced acute lung injury and sepsis‑associated lethality. Although the role of HMGB1 in endothelial cell cytoskeletal rearrangement and vascular permeability have been investigated preliminarily, the molecular mechanisms remain to be fully elucidated. As the ras‑related C3 botulinum toxin substrate 1 (Rac1) gene is important role in regulating microvascular barrier maintenance, the present study was designed to determine whether Rac1 is involved in HMGB1‑induced hyperpermeability in pulmonary microvascular endothelial cells (PMVECs). The results of the present study demonstrated that HMGB1 induced dose and time‑dependent decreases in transendothelial electrical resistance (TER). Notably, HMGB1 induced a dose‑dependent increase in the activity and expression levels of Rac1. Using small interfering RNA and an agonist of Rac1, the present study demonstrated that Rac1 was a novel factor mediating the HMGB1‑induced decrease in TER via extracellular signal‑regulated kinase and p38 mitogen‑activated protein kinase (MAPK) activation. These data suggested that Rac1 is involved in HMGB1‑induced hyperpermeability in PMVECs via MAPK signal transduction.
authors.affiliation: Department of Critical Care Medicine, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Shao
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Tang
authors.affiliation: Department of Critical Care Medicine, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Hua-Qing
authors.initials: HQ
authors.lastname: Zhu
mesh_terms: D002199:Capillary Permeability / Q000187:drug effects*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D024243:HMGB1 Protein / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D055806:Microvessels / Q000166:cytology*; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D020830:rac1 GTP-Binding Protein