title: A Novel Role of OS-9 in the Maintenance of Intestinal Barrier Function from Hypoxia-induced Injury via p38-dependent Pathway.
abstract: OS-9 is a lectin required for efficient ubquitination of glycosylated substrates of endoplasmic reticulum-associated degradation (ERAD). OS-9 has previously been implicated in ER-to-Golgi transport and transcription factor turnover. However, we know very little about other functions of OS-9 under endoplasmic reticulum stress. Here, we used gene knockdown and overexpression approaches to study the protective effect of OS-9 on intestinal barrier function of intestinal epithelial cell Caco-2 monolayer. We found that OS-9 attenuated intestinal epithelial barrier dysfunction under hypoxia through up-regulating occludin and claudin-1 protein expression. Furthermore, we showed that the up-regulation of occludin and claudin-1 induced by OS-9 was mediated by p38 and ERK1/2 phosphorylation and did not involve HIF-1α. In summary, our results demonstrate that OS-9 up-regulates occludin and claudin-1 by activating the MAP kinase (MAPK) pathway, and thus protects the epithelial barrier function of Caco-2 monolayer under hypoxia condition.
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Songwei
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D018938:Caco-2 Cells; D015687:Cell Hypoxia; D062445:Claudin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology; D007422:Intestines / Q000502:physiology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D010766:Phosphorylation; D019108:Tight Junctions / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation
chemical_list: D062445:Claudin-1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D037102:Lectins; D009363:Neoplasm Proteins; C098898:OS9 protein, human; D062793:Occludin
keywords: OS-9; intestinal epithelial barrier; p38; tight junction