Increased expression of lung TRPV1/TRPA1 in a cough model of bleomycin-induced pulmonary fibrosis in Guinea pigs

Abstract

Background: Chronic cough is a difficult-to-treat comorbidity of idiopathic pulmonary fibrosis (IPF), and significantly impacts on the quality of life of patients with IPF. Transient receptor potential (TRP) channel proteins may play an important role in chronic cough. However, expression of these proteins in lung of IPF is largely unknown. Methods: Guinea pig model of pulmonary fibrosis was established by single intratracheal delivery of bleomycin. Respiratory ungated micro-CT scans were performed on days 7, 14, 21 and 28 to assess progression of pulmonary fibrosis. Cough sensitivity to capsaicin was evaluated in conscious animals on days 13 and 27. Real-time PCR (qPCR) and immunohistochemistry were employed to measure expression of TRPV1 and TRPA1 in lung tissue. Results: Micro-CT showed that lung consolidation was detectable from day 7 distributing mainly in the middle and lower lung fields, which was significantly correlated to Ashcroft fibrosis score (r = 0.7993, p < 0.001). Cough sensitivity to capsaicin in bleomycin-treated animals was significantly increased on days 13 and 27. qPCR showed that expression of TRPV1 and TRPA1 was positively correlated each other and significantly upregulated in lung tissues of model group compared with that of controls, which was further supported by immunohistochemistry. Furthermore, immunoreactivity for TRPV1 and TRPA1 was negatively correlated with Ashcroft fibrosis score. Conclusion: Expression of TRPV1/TRPA1 was upregulated in the chronic cough related to bleomycin induced pulmonary fibrosis in guinea pigs, which provided new insights into the mechanism of IPF-associated cough hypersensitivity. Micro-CT is very helpful methodology to access pulmonary fibrosis progression in small animal models.