XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury
| Autor: | Tereza Tomankova, Hae Ra Cho, Yingchun Wang, Hiroaki Toba, Zhehong Guan, Feng Tian, Shaf Keshavjee, Mingyao Liu, Xiao-Hui Bai, Oyedele Adeyi |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Lipopolysaccharide septic response Acute Lung Injury Lung injury Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sepsis medicine Animals Adaptor Proteins Signal Transducing XB130 Mice Knockout Lung business.industry Monocyte Microfilament Proteins inflammatory response 3. Good health transgenic mouse cell death cell proliferation 030104 developmental biology medicine.anatomical_structure Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Immunology Cancer cell Tumor necrosis factor alpha business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Hiroaki Toba 1 , Tereza Tomankova 1 , Yingchun Wang 1 , Xiaohui Bai 1 , Hae-Ra Cho 1 , Zhehong Guan 1 , Oyedele A. Adeyi 2 , Feng Tian 1 , Shaf Keshavjee 1, 3, 4 , Mingyao Liu 1, 3, 4 1 Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, Universal Health Network, University of Toronto, Toronto, Ontario, Canada 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada 3 Department of Surgery, University of Toronto, Toronto, Ontario, Canada 4 Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada Correspondence to: Mingyao Liu, e-mail: mingyao.liu@utoronto.ca Keywords: cell death, cell proliferation, inflammatory response, septic response, transgenic mouse Received: August 31, 2015 Accepted: March 08, 2016 Published: March 23, 2016 ABSTRACT XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability. |
| Databáze: | OpenAIRE |
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