@article {BauerP3930, author = {Carla Bauer and Davide Botta and Ruoqi Peng and Gaurav Tyagi and Jonathan Phillips and Paul Harris and Lorena Renteria and Lisa Burns and Frances Lund and Christopher Stevenson}, title = {A transient receptor potential melastin-2 deficiency significantly worsens the fibrotic response to bleomycin in mice}, volume = {42}, number = {Suppl 57}, elocation-id = {P3930}, year = {2013}, publisher = {European Respiratory Society}, abstract = {The transient receptor potential melastin-2 (TRPM-2) is a nonselective and redox-sensitive cation channel that is expressed in a number of inflammatory cells and plays a role in sensing oxidative stress. Given the role oxidative stress plays in the pathogenesis of idiopathic pulmonary fibrosis (IPF), we tested our hypothesis that inhibiting TRPM-2 function may delay the progression of this disease using the mouse model of bleomycin-induced pulmonary fibrosis. 35\% of TRPM-2-deficient mice challenged with bleomycin (2U/kg) reached endpoint compared to none of the wild-type mice. Bleomycin-challenged TRPM-2-deficient mice had significantly higher Ashcroft scores, which were associated with increased myofibroblast accumulation in the lungs of these animals. Functionally, bleomycin-challenged TRPM-2-deficient mice had significantly greater measures of tissue elastance and reduced forced vital capacity compared to controls, as assessed using the Scireq flexivent system. Finally, lung CT image analysis revealed that the fibrotic response observed in TRPM-2-deficient mice was more wide-spread than observed in wild-type mice.Contrary to our hypothesis, these data suggest that pharmacological activation of TRPM-2 may be protective in IPF.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/P3930}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/P3930.full.pdf}, journal = {European Respiratory Journal} }