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Glycogen synthase kinase‑3β inhibitor reduces LPS‑induced acute lung injury in mice. 2017

Qi Ding, and Gaoqin Liu, and Yuanyuan Zeng, and Jianjie Zhu, and Zeyi Liu, and Junhong Jiang, and Jianan Huang
Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Jiangsu 215006, P.R. China.

The aim of the present study was to examine the role of Wnt signaling in lipopolysaccharide (LPS)‑induced acute respiratory distress syndrome (ARDS). ARDS was induced by LPS and compared in mice treated with either glycogen synthase kinase‑3β inhibitor (GSKI) or PBS. The protein expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, IL‑17, IL‑18 and IL‑1β in the bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific enzyme‑linked immunosorbent assays. The accumulation of neutrophils and macrophages in the BALF were detected using flow cytometry. The extent of pathological lesions was evaluated using an immunohistochemical assay. The differentiation of mesenchymal stem cells (MSCs) into type II alveolar (ATII) epithelial cells was analyzed using immunofluorescence staining. Treatment with GSKI led to maintained body weights and survival in mice with LPS‑induced ARDS. Treatment with GSKI effectively reduced the levels of total protein, albumin, IgM and keratinocyte growth factor in the BALF. Smith scores showed that GSKI significantly alleviated LPS‑induced lung injury. GSKI also functioned to reduce inflammatory cell accumulation and pro‑inflammatory cytokine secretion. Finally, it was found that GSKI promoted the differentiation of MSCs into ATII epithelial cells in vivo. Taken together, the GSKI‑treated mice exhibited reduced acute lung injury through inhibited intra‑fluid inflammatory cell infiltration and decreased expression of pro‑inflammatory cytokines, and GSKI increased the differentiation of MSCs into ATII epithelial cells.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000071679 Glycogen Synthase Kinase 3 beta A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER. GSK-3beta,GSK3B Protein,GSK3beta,GSK 3beta
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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