title: Enforced expression of miR-125b attenuates LPS-induced acute lung injury.
abstract: The acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Recent evidence implicated a potential role of miR-125b in development of ALI. Here we evaluated the miR-125b-based strategy in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We found that up-regulation of miR-125b expression maintained the body weight and survival of ALI mice, and significantly reduced LPS-induced pulmonary inflammation as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Further, enforced expression of miR-125b resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin and IgM in BAL fluid, and ameliorated the histopathology changes of lung in LPS-induced ALI mice. Of interest, serum miR-125b expression was also decreased and inversely correlated with the disease severity in patients with ARDS. Our findings strongly demonstrated that enforced expression of miR-125b could effectively ameliorate the LPS-induced ALI, suggesting a potential application for miR-125b-based therapy to treat clinical ARDS.
authors.affiliation: Department of VIP, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of VIP, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kailing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: rentaosh@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010539:Permeability; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D035683:MicroRNAs
keywords: Acute lung injury; Acute respiratory distress syndrome; miR-125b