An age-wise comparison of human airway smooth muscle proliferative capacity

• Published in: PloS one 2015-03, Vol.10 (3), p.e0122446-e0122446
• Main Authors: Fayon, Michael, Andrieux, Annick, Bara, Imane, Rebola, Muriel, Labbé, André, Marthan, Roger, Berger, Patrick
• Format: Article
• Language: English
• Subjects: Adult; Adults; Age; Aged; Apoptosis; Asthma; Biosynthesis; Calcium; Calcium (intracellular); Calcium (mitochondrial); Calcium - metabolism; Calcium homeostasis; Calcium ions; Calcium Signaling; CCAAT-Enhancer-Binding Proteins - metabolism; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Comparative analysis; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA biosynthesis; DNA synthesis; Environmental conditions; Female; Fetal calf serum; Glucose; Glucose - pharmacology; Glucose metabolism; Glycolysis; Histamine; Homeostasis; Humans; Infant, Newborn; Lung diseases; Lung Diseases - metabolism; Lung Diseases - pathology; Male; Middle Aged; Mitochondria; Mitochondria - metabolism; Muscles; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Neonates; Newborn babies; Ostomy; Pediatrics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Platelet-derived growth factor; Platelet-Derived Growth Factor - pharmacology; Porins; Respiratory tract; Smooth muscle; Transcription factors; Transcription Factors - metabolism; TRPC Cation Channels - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0122446

We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS) and PDGF-AA. In the presence of glucose, cell counts were significantly greater in neonatal vs. adult ASMC. Similarly, neonatal ASMC DNA synthesis in 10% FCS and PDGF-AA, and [Ca2+]i responses in the presence of histamine were significantly enhanced vs. adults. In glucose-free medium, cell proliferation was preserved in neonatal cells, unlike in adult cells, with concomitant increased porin (an indicator of mitochondrial activity) protein expression. Compared to adults, stimulated neonatal human ASMC are in a rapid and robust proliferative phase and have the capacity to respond disproportionately under abnormal environmental conditions, through increased mitochondrial biogenesis and altered calcium homeostasis.