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Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle
Published on: May 5, 2022
An age-wise comparison of human airway smooth muscle proliferative capacity
Michael Fayon1, Annick Andrieux1, Imane Bara2
1Université de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, F-33000, Bordeaux, France; CHU de Bordeaux, Hôpital Pellegrin-Enfants, Pneumologie Pédiatrique, Centre d'Investigation Clinique (CIC 1401), F-33076, Bordeaux, France.
Insights
Neonatal airway smooth muscle cells (ASMC) show greater proliferation and enhanced responses compared to adult ASMC, especially under altered metabolic conditions. This highlights their robust proliferative capacity and unique adaptability.
Area of Science:
- Cell Biology
- Respiratory Medicine
- Metabolic Physiology
Background:
- Airway smooth muscle cells (ASMC) play a crucial role in airway function and disease.
- Differences in ASMC proliferation and function between neonatal and adult stages are not fully understood.
- Metabolic state can significantly influence cell behavior and energy production pathways.
Purpose of the Study:
- To compare the proliferative capacity and functional responses of neonatal versus adult ASMC.
- To investigate the impact of glucose availability on ASMC proliferation and mitochondrial activity.
- To explore the role of altered environmental conditions on ASMC behavior.
Main Methods:
- ASMC from neonatal and adult donors (no/moderate lung disease) were cultured in glucose-containing or glucose-free media.
- Cell proliferation, DNA synthesis, and intracellular calcium ([Ca2+]i) responses were measured.
- Porin protein expression, an indicator of mitochondrial activity, was assessed.
Main Results:
- Neonatal ASMC exhibited significantly greater cell counts and DNA synthesis than adult ASMC in the presence of glucose.
- Enhanced [Ca2+]i responses to histamine were observed in neonatal ASMC compared to adults.
- Cell proliferation was maintained in neonatal ASMC but reduced in adult ASMC in glucose-free medium, with increased porin expression in neonatal cells.
Conclusions:
- Stimulated neonatal human ASMC are in a rapid proliferative phase with enhanced functional responses compared to adults.
- Neonatal ASMC demonstrate a greater capacity to adapt to altered environmental conditions, utilizing mitochondrial pathways.
- Increased mitochondrial biogenesis and altered calcium homeostasis contribute to the distinct behavior of neonatal ASMC.
Abstract:
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.
