LRP1 In MEchanically ventilated adults STudy (LIME ST)
Research type
Research Study
Full title
Role of cell-surface endocytic receptor LRP1 and its ectodomain shedding in respiratory health and disease
IRAS ID
297777
Contact name
Kazuhiro Yamamoto
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
1 years, 10 months, 30 days
Research summary
According to the British Lung Foundation an estimated 10,000 people in the UK are diagnosed with a lung disease every week and Liverpool is reported to have some of the highest rates in the country. COPD and pulmonary fibrosis are some of the a long-term lung diseases that can have a significant impact on a person’s quality of life. However, there is no cure for these conditions mainly due to insufficient knowledge of molecular events associated with the disease progression. In addition, 2020 has seen a huge rise in lung problems due to the effect of the novel coronavirus SARS COV2 and the COVID pandemic. This can acutely affect the lungs, causing and acute pneumonitis leading to acute respiratory failure, the need for invasive ventilation, high mortality and in survivors potential long term lung scarring and fibrosis. The molecular pathways leading to these outcomes are unknown and require further research. Medical therapies of potential benefit include immunomodulatory ones such as dexamethasone, and tocilizumab, the mechanisms for these benefits are unknown.
LRP1 is a ubiquitously expressed, versatile cell surface transmembrane receptor involved in adult tissue homeostasis. It binds to and mediates endocytosis of a variety of molecules. In 2011, Soler Artigas et al identified LRP1 as a gene relevant for lung function by the large genome-wide association with meta-analysis. However, role of LRP1 in lung diseases has hardly been explored. We have recently discovered that increased ectodomain shedding of LRP1 shifts homeostatic matrix turnover to a catabolic state. We thus hypothesised that LRP1 shedding is increased in pathological conditions of the respiratory system. We will test this hypothesis by measuring quantity of soluble shed form of LRP1 and LRP1 ligands in human clinical samples.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
21/NW/0324
Date of REC Opinion
18 Jan 2022
REC opinion
Further Information Favourable Opinion