title: KyoT2 downregulates airway remodeling in asthma.
abstract: The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical UniversityXi'an 710032, China; Department of Respiratory Medicine, 306 Hospital of PLABeijing 100101, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Ou-Yang
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China.
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Ti
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University Xi'an 710032, China.
authors.forename: Chang-Gui
authors.initials: CG
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D056151:Airway Remodeling; D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005355:Fibrosis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D060588:LIM Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C486306:Fhl1 protein, mouse; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse
keywords: KyoT2; airway hyperresponsiveness (AHR); airway remodeling
references.citation: Respiration. 2013;86(4):341-6
references.pmid: 23860410
references.citation: Chin Med J (Engl). 2005 Dec 5;118(23):1959-64
references.pmid: 16336831
references.citation: Cell. 2004 Dec 17;119(6):815-29
references.pmid: 15607978
references.citation: Exp Biol Med (Maywood). 2014 Dec;239(12):1589-96
references.pmid: 25107895
references.citation: J Gene Med. 2006 Dec;8(12):1393-9
references.pmid: 17019745
references.citation: Eur Respir J. 2008 Jan;31(1):143-78
references.pmid: 18166595
references.citation: Am J Respir Crit Care Med. 2009 May 15;179(10):875-82
references.pmid: 19234107
references.citation: Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L411-9
references.pmid: 19542246
references.citation: J Immunol. 2009 Oct 1;183(7):4745-54
references.pmid: 19752226
references.citation: Curr Allergy Asthma Rep. 2009 Nov;9(6):475-83
references.pmid: 19814921
references.citation: Nature. 2009 Nov 12;462(7270):182-8
references.pmid: 19907488
references.citation: Discov Med. 2011 Apr;11(59):283-91
references.pmid: 21524382
references.citation: Biochem Biophys Res Commun. 2002 Mar 1;291(3):582-7
references.pmid: 11855828
references.citation: Gene Ther. 2004 Oct;11(20):1497-505
references.pmid: 15269717
references.citation: J Exp Med. 1996 Jan 1;183(1):109-17
references.pmid: 8551213
references.citation: Mol Cell Biol. 1998 Jan;18(1):644-54
references.pmid: 9418910
references.citation: Exp Biol Med (Maywood). 2011 Dec;236(12):1461-7
references.pmid: 22114062
references.citation: Int Arch Allergy Immunol. 2012;157(1):65-72
references.pmid: 21912175
references.citation: Adv Exp Med Biol. 2012;727:89-98
references.pmid: 22399341
references.citation: Wound Repair Regen. 2012 Sep-Oct;20(5):688-706
references.pmid: 22985040
references.citation: Pulm Pharmacol Ther. 2013 Feb;26(1):24-36
references.pmid: 22967819
references.citation: PLoS One. 2013;8(5):e63896
references.pmid: 23704950
references.citation: Int J Immunopathol Pharmacol. 2013 Apr-Jun;26(2):371-81
references.pmid: 23755752
references.citation: Curr Opin Pharmacol. 2013 Jun;13(3):324-30
references.pmid: 23639507
references.citation: PLoS One. 2013;8(7):e68685
references.pmid: 23874722
references.citation: Lab Invest. 2013 Nov;93(11):1219-31
references.pmid: 24042439