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, Mingyao Liu

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)25420-25431
Number of pages12
JournalOncotarget
Volume7
Issue number18
DOIs
StatePublished - May 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Canadian Institutes of Health Research (CIHR) operating grants MOP-13270, MOP-42546 and MOP-119514.

Keywords

  • Cell death
  • Cell proliferation
  • Inflammatory response
  • Septic response
  • Transgenic mouse

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