Mesothelial cell derived TGFbeta and its role in adhesive serosal disease.
Dr Rachel Chambers
Description of Project:
Pleural adhesions are a common complication of parapneumonic effusions, and empyema, contributing significantly to the morbidity of these conditions. In the health state, mesothelial cells are responsible for the maintenance of the microenvironment, and non-adhesive properties of serosal cavities. However, following insult, and during inflammation, the pleural, pericardial and peritoneal cavities are highly susceptible to adhesion formation and fibrosis. We are interested in the contribution of mesothelial cells to the profibrotic environment of the pleural cavity by TGFβ production and activation, leading to extracellular matrix deposition.
Coagulation proteins have an established role in lung fibrosis, and in peritoneal adhesion formation, in terms of fibrin deposition, and fibrinolytics have been used during empyema to assist drainage of the prurulent fluid. Coagulation proteins, such as thrombin, can also exert effects through a set of receptors known as Protease Activated Receptor (PAR)s. During this project I have investigated the role of the mesothelial cell response to thrombin in TGFβ production and activation.
Mutsaers SE, Kalomenidis I, Wilson NA, Lee YCG. Growth Factors in Pleural Fibrosis. Current Opinion in Pulmonary Medicine 2006; 12: 251-258.