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Tensin1 expression and function in chronic obstructive pulmonary disease

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posted on 2020-04-23, 10:32 authored by Panayiota Stylianou, Katherine Clark, Bibek Gooptu, Dawn Smallwood, Christopher E Brightling, Yassine Amrani, Katy M Roach, Peter Bradding

Chronic 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.

Funding

This work was supported by the National Institute for Health Research Leicester Respiratory Biomedical Research Unit (PhD studentship, PS). BG’s research is supported by the Medical Research Council (UK), and the British Lung Foundation.

History

Citation

Scientific Reports, 2019, 9, 18942

Author affiliation

College of Life Sciences

Version

  • VoR (Version of Record)

Published in

Scientific Reports

Volume

9

Issue

1

Publisher

Nature Research

eissn

2045-2322

Acceptance date

2019-11-25

Copyright date

2019

Publisher version

https://www.nature.com/articles/s41598-019-55405-2#Abs1

Language

en

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