title: Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.
abstract: The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Mayra
authors.initials: M
authors.lastname: Álvarez-Santos
authors.affiliation: Departamento de Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Verónica
authors.initials: V
authors.lastname: Carbajal
authors.affiliation: Departamento de Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Olivia
authors.initials: O
authors.lastname: Tellez-Jiménez
authors.affiliation: Departamento de Enfermedades Crónico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Martínez-Cordero
authors.affiliation: Laboratorio de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Victor
authors.initials: V
authors.lastname: Ruiz
authors.affiliation: Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga 15, México DF, 14000, México.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Departamento de Bioquímica, Universidad Nacional Autónoma de México, México DF, 70159, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lascurain
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santibañez-Salgado
authors.affiliation: Departamento de Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlapan 4502, Col. Sección XVI, México DF, 14080, México.
authors.forename: Blanca
authors.initials: B
authors.lastname: Bazan-Perkins
mesh_terms: D056151:Airway Remodeling / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D022001:Focal Adhesions / Q000378:metabolism*; D006168:Guinea Pigs; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051419:Paxillin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016608:Talin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D019012:Integrin beta1; D051419:Paxillin; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016608:Talin; D000099200:Scaffold Protein ILK
keywords: AIRWAY; AIRWAY SMOOTH MUSCLE; ASTHMA; HYPERRESPONSIVENESS; INTEGRIN-LINKED KINASE; PAXILLIN; TALIN; β1 INTEGRIN