Osteopontin Deficiency Protects against Airway Remodeling and Hyperresponsiveness in Chronic Asthma

Camargo Madeira Simoes, Davina, Xanthou, Georgina, Petrochilou, Kalomira, Panoutsakopoulou, Vily, Roussos, Charis and Gratziou, Christina (2009) Osteopontin Deficiency Protects against Airway Remodeling and Hyperresponsiveness in Chronic Asthma. American Journal of Respiratory and Critical Care Medicine, 179 (10). pp. 894-902. ISSN 1073-449X

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Abstract

Rationale: Osteopontin (OPN) is a cytokine that is upregulated in epithelial cells and macrophages in the lungs of mice during chronic allergen challenge and airway remodeling and also in lungs of patients with asthma. However, it remains unclear whether OPN has an in vivo effect on lung remodeling in allergic asthma. Based on its ability to induce smooth muscle and fibroblast proliferation and migration we hypothesize that OPN regulates lung remodeling and also affects subsequent airway hyperresponsiveness (AHR).

Objectives: Study the role of OPN in airway remodeling using OPN-knockout (KO) mice and a reversal approach administering recombinant mouse OPN (rOPN) in KO mice before challenge.

Methods: A chronic allergen-challenge model of airway remodeling with OPN KO mice, KO mice treated with rOPN, and human bronchial smooth muscle were used.

Measurements and Main Results: OPN deficiency protected mice against ova-induced AHR, which was associated with lower collagen and mucus production, gob-5 mRNA expression, submucosal cell area infiltration, and proliferation. Administration of rOPN to KO mice, just at the final five allergen challenges, exacerbated AHR and all the remodeling characteristics measured. In addition, rOPN increased the expression of IL-13 and pro–matrix metalloproteinase-9 in the lungs. Moreover, we demonstrated that rOPN induces proliferation of human BSM through binding to its αvβ3 integrin receptor and activation of PI3K/Akt downstream signaling pathway.

Conclusions: We conclude that OPN deficiency protects against remodeling and AHR. Thus our data reveal OPN as a novel therapeutic target for airway remodeling and associated AHR in chronic asthma.

Item Type:	Article
Uncontrolled Keywords:	osteopontin, human smooth muscle cells, remodeling asthma
Subjects:	B100 Anatomy, Physiology and Pathology C700 Molecular Biology, Biophysics and Biochemistry
Department:	Faculties > Health and Life Sciences > Sport, Exercise and Rehabilitation
Depositing User:	Becky Skoyles
Date Deposited:	19 Dec 2017 09:56
Last Modified:	12 Oct 2019 11:47
URI:	http://nrl.northumbria.ac.uk/id/eprint/32896

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