title: Phosphatidylinositol 3-Kinase Mediates β-Catenin Dysfunction of Airway Epithelium in a Toluene Diisocyanate-Induced Murine Asthma Model.
abstract: Cell-cell junctions are critical for the maintenance of cellular as well as tissue polarity and integrity. Yet the role of phosphatidylinositol 3-kinase (PI3K) in dysregulation of airway epithelial adherens junctions in toluene diisocyanate (TDI)-induced asthma has not been addressed. Male BALB/c mice were first dermally sensitized and then challenged with TDI by means of compressed air nebulization. The mice were treated intratracheally with PI3K inhibitor LY294002. Levels of phospho-Akt in airway epithelium and whole lung tissues were markedly increased in TDI group compared with control mice, which decreased after administration of LY294002. The dilated intercellular spaces of airway epithelium induced by TDI were partially recovered by LY294002. Both the protein expression and distribution of adherens junction proteins E-cadherin and β-catenin were altered by TDI. Treatment with LY294002 rescued the distribution of E-cadherin and β-catenin at cell-cell membranes, restored total β-catenin pool, but had no effect on protein level of E-cadherin. At the same time, LY294002 also inhibited phosphorylation of ERK, glycogen synthase kinase3β and tyrosine 654 of β-catenin induced by TDI. In summary, our results showed that the PI3K pathway mediates β-catenin dysregulation in a TDI-induced murine asthma model, which may be associated with increased tyrosine phosphorylation of β-catenin.
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yao
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and.
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and.
authors.forename: Haixiong
authors.initials: H
authors.lastname: Tang
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Song
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and.
authors.forename: Hangming
authors.initials: H
authors.lastname: Dong
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: *Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; and caishaox@fimmu.com.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*; D051176:beta Catenin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015820:Cadherins; D002867:Chromones; D004791:Enzyme Inhibitors; D007378:Interleukins; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014051:Toluene 2,4-Diisocyanate; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: PI3K; adherens junctions; asthma; toluene diisocyanate; β-catenin