Tensin1 expression and function in chronic obstructive pulmonary disease

Abstract

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.

Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial–mesenchymal transition

“…It has been accepted that one of the principal causes for airflow limitation in COPD is the airway wall tissue remodelling through re-organisation of the ECM [ 18 ]. In the current study, we analysed two important markers of ECM pathology, collagen-1 and fibronectin, both of which have been described as colocalised to areas with increased proliferation of myofibroblasts in COPD [ 19 , 20 ]. Although we found significant increases in percent expression of both these ECMs, there were also marked differences between fibronectin and collagen-1 expression in various SA sublayers.…”

The Roles of Pseudophosphatases in Disease

“…Pseudophosphatases are important regulators, and their proper regulation is important for maintaining homeostasis and preventing diseases [5]. Mutations of these molecules or their misregulation leads to diseases such as leukemia, breast cancer, colorectal cancer, hepatocarcinoma, glioblastoma, other cancers, Charcot-Marie-Tooth (CMT) disease (abnormal nerve myelination), obesity, diabetes, chronic obstructive pulmonary disease (COPD), and nephrotic syndrome [5,7,[27][28][29][30][31][32][33]. A comprehensive list of the known functions of pseudophosphatases and their implications in diseases is provided in Table 1.…”

“…A tensin 1 single nucleotide polymorphism (SNP) at position 1197 from an arginine to a tryptophan (R1197W) correlates with an increase in COPD. TGFβ1 upregulates the expression of mutated (R1197W) tensin 1, increasing α smooth muscle actin (αSMA) expression (Figure 4(Ai)) [32]. αSMA is a major component of human airway smooth muscle cells (HASMCs).…”

“…αSMA is a major component of human airway smooth muscle cells (HASMCs). Therefore, an increase in αSMA expression increases airway smooth muscle (ASM), possibly contributing to the characteristic airway thickening of COPD (Figure 4(Ai)) [32]. Tensin 1 is also linked to human colorectal cancer (Figure 4(Aii)).…”

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

“…The complex pathogenesis of COPD involves protease-antiprotease imbalance, oxidative stress and chronic inflammation. The disease is characterized by irreversible airway remodeling that involves thickening of the airway wall and the airway smooth muscle (ASM) layer, mucus hypersecretion and epithelial cells metaplasia [ 3 ]. Thus, COPD is also regarded as a muco-obstructive disease accompanied by increased amounts of mucin, particularly MUC5AC that may uniquely modify mucus properties [ 4 ].…”