Role of mitochondrial biogenesis in asthmatic airway smooth muscle proliferation: Forever young

Abstract

Introduction Increased bronchial smooth muscle mass is one of the key structural features of severe asthma. In adults, asthmatic airway smooth muscle cells (ASMC) demonstrate greater mitochondrial biogenesis associated with an increase in ASMC proliferation rate vs. non-asthmatic ASMC. However, to the best of our knowledge, there is no evidence that such a difference between asthmatic and non-asthmatic ASMC occurs in pre-school children. Thus, the primary aim of the study was to compare asthmatic and non-asthmatic ASMC proliferation and mitochondrial biogenesis in adults and pre-school children. The secondary aim was to assess the effect of factors released by the epithelium upon stimulation by environmental factors such as house dust mite and rhinovirus, on ASMC proliferation. Methods We cultured ASMC and bronchial epithelial cells (BEC) obtained by endobronchial biopsy from children and adults with severe asthma or undergoing bronchial endoscopy for other reasons. We then studied ASMC proliferation (cell counting and CFSE dye assay) in 10% fetal bovine serum (FBS), 0% FBS and after the addition of the BEC culture supernatant obtained after rhinovirus infection, house dust mite exposure or both. Mitochondrial mass and biogenesis were determined by western blot. Results Sixteen pre-school children with severe asthma,median aged 2.8 years, 4 control children (4.6 years), 13 adults with severe asthma (46.0 years) and 26 controls adults (65.3 years) were included. ASMC proliferation was increased in asthmatic adults, asthmatic pre-school and control children ASMC vs. control adults, with a cell doubling time of 35.0 ± 2.5 h, 24.8 ± 1.9 h, 22.6 ± 2.6 h and 47.4 ± 4.4 h, respectively ( P Conclusion As previously described in adult asthmatics, ASMC proliferation is enhanced in both asthmatic and non-asthmatic children. This is associated with an increase in mitochondrial mass and biogenesis. ASMC proliferation is increased after a viral infection or an allergen exposure.