Tensin1 expression and function in chronic obstructive pulmonary disease

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dc.cclicenceN/Aen
dc.contributor.authorStylianou, P.
dc.contributor.authorClark, K.
dc.contributor.authorGooptu, B.
dc.contributor.authorSmallwood, Dawn T.
dc.contributor.authorBrightling, C. E.
dc.contributor.authorAmrani, Y.
dc.contributor.authorRoach, K.M.
dc.contributor.authorBradding, Peter
dc.date.acceptance2019-11-25
dc.date.accessioned2020-01-23T08:46:28Z
dc.date.available2020-01-23T08:46:28Z
dc.date.issued2019-12-12
dc.descriptionopen access articleen
dc.description.abstractChronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.en
dc.funderNIHR (National Institute for Health Research)en
dc.funder.otherBritish Lung Foundationen
dc.funder.otherMedical Research Council (UK)en
dc.identifier.citationStylianou, P., Clark, K., Gooptu, B., Smallwood, D.T., Brightling, C.E., Amrani, Y., Roach, K.M., Bradding, P. (2019) Tensin1 expression and function in chronic obstructive pulmonary disease. Scientific Reports,9, 18942.en
dc.identifier.doihttps://doi.org/10.1038/s41598-019-55405-2
dc.identifier.issn2045-2322
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/19051
dc.language.isoen_USen
dc.peerreviewedYesen
dc.projectidN/Aen
dc.projectidN/Aen
dc.publisherSpringer Natureen
dc.researchinstituteInstitute for Allied Health Sciences Researchen
dc.subjectTensin1en
dc.subjectchronic obstructive pulmonary diseaseen
dc.subjecthuman airway smooth muscle cellsen
dc.subjectTNS1 geneen
dc.titleTensin1 expression and function in chronic obstructive pulmonary diseaseen
dc.typeArticleen

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