ABSTRACT
The formation of healthy tissue involves continuous remodeling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here, we examine how tensin3 contributes to the formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors such as talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for the formation of α5ß1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.
Subject(s)
Fibronectins , Focal Adhesions , Talin , Tensins , Cell Adhesion , Extracellular Matrix/metabolism , Fibronectins/genetics , Fibronectins/metabolism , Focal Adhesions/genetics , Focal Adhesions/metabolism , Integrins/metabolism , Talin/genetics , Talin/metabolism , Tensins/genetics , Tensins/metabolism , Vinculin/genetics , Vinculin/metabolismABSTRACT
Background: There is no standardized international model for specialist lymphedema services, which covers the types of lymphedema treated and the treatments provided. The aim of this study was to provide a profile of patients attending specialist lymphedema services in different countries to explore similarities and differences. Methods and Results: The LIMPRINT core tool was used in specialist lymphedema services in the United Kingdom, France, Italy, and Turkey. Services in Turkey saw a slightly younger age group, with a higher proportion of female patients reflecting a particular focus on breast cancer-related lymphedema. There were higher levels of obesity and restricted mobility in patients in the United Kingdom compared with other countries. Italy and France saw the highest percentage of patients with primary lymphedema. Diabetes was a common comorbidity in the United Kingdom and Turkey. The United Kingdom saw the largest number of patients with lower limb lymphedema. Conclusions: The results show a wide range of complexity of patients treated in specialist lymphedema services. Some of the differences between countries may reflect different stages in the evolution of specialist lymphedema services, rather than a true difference in prevalence, with those with "younger" services treating a high proportion of patients with cancer and those with more established services treating a wider range of different types of lymphedema, including more elderly people with multiple comorbidities.
Subject(s)
Breast Neoplasms/diagnosis , Cellulitis/diagnosis , Edema/diagnosis , Lymphatic System/pathology , Lymphedema/diagnosis , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Cellulitis/epidemiology , Cellulitis/pathology , Cellulitis/physiopathology , Child , Child, Preschool , Chronic Disease , Diabetes Mellitus/diagnosis , Diabetes Mellitus/physiopathology , Diagnosis, Differential , Edema/epidemiology , Edema/pathology , Edema/physiopathology , Female , France/epidemiology , Humans , Italy/epidemiology , Lower Extremity/pathology , Lower Extremity/physiopathology , Lymphatic System/physiopathology , Lymphedema/epidemiology , Lymphedema/pathology , Lymphedema/physiopathology , Male , Middle Aged , Neurocognitive Disorders/diagnosis , Neurocognitive Disorders/physiopathology , Obesity, Morbid/diagnosis , Obesity, Morbid/physiopathology , Practice Guidelines as Topic , Prevalence , Risk Factors , Turkey/epidemiology , United Kingdom/epidemiologyABSTRACT
Background and Study Design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic edema (CO) and its impact on health services. Overall 7436 with CO were recruited in the main UK study from a range of health settings. Methods and Results: Factors relating to subjective control of arm and leg CO were defined in the UK. A total of 1565 patients were included in the study with exclusions for: no limb swelling or not recorded (1669), having concurrent arm/leg CO (272), control of assessment missing (5) and professional being unsure of control status of CO (325). Arm swelling occurred in 953 (18.5%) with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.2%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were : obesity, neurological disease and cellulitis in the last year and for leg CO, obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialized centers is complex due to sociodemographic and clinical comorbidities.
