Oncotarget

Research Papers:

XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury

Hiroaki Toba, Tereza Tomankova, Yingchun Wang, Xiaohui Bai, Hae-Ra Cho, Zhehong Guan, Oyedele A. Adeyi, Feng Tian, Shaf Keshavjee and Mingyao Liu _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:25420-25431. https://doi.org/10.18632/oncotarget.8326

Metrics: PDF 2980 views  |   HTML 2063 views  |   ?  


Abstract

Hiroaki Toba1, Tereza Tomankova1, Yingchun Wang1, Xiaohui Bai1, Hae-Ra Cho1, Zhehong Guan1, Oyedele A. Adeyi2, Feng Tian1, Shaf Keshavjee1,3,4, Mingyao Liu1,3,4

1Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, Universal Health Network, University of Toronto, Toronto, Ontario, Canada

2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

3Department of Surgery, University of Toronto, Toronto, Ontario, Canada

4Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Correspondence to:

Mingyao Liu, e-mail: [email protected]

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8326