Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism.
Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Di
D
Qi
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xumao
X
Tang
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jing
J
He
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Daoxin
D
Wang
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Yan
Y
Zhao
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wang
W
Deng
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xinyu
X
Deng
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Guoqi
G
Zhou
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jing
J
Xia
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xi
X
Zhong
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Shenglan
S
Pu
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002116:Calcitonin / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015398:Signal Transduction; D016019:Survival Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D002116:Calcitonin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt