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Updated: Sep 28, 2026
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Oxygen regulates mitogen-stimulated proliferation of fetal human airway smooth muscle cells
Hitesh C Pandya1, Vladimir A Snetkov, Charles H C Twort
1Department of Respiratory Medicine and Allergy, The Guy's, King's, and St. Thomas' School of Medicine, King's College London, London SE1 9RT, United Kingdom.
Insights
Premature infants with lung disease experience increased airway smooth muscle (ASM) due to oxygen exposure. Reactive oxygen species (ROS) mediate this proliferation, influenced by oxygen levels and growth factors.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Neonatology
Background:
- Infants with bronchopulmonary dysplasia exhibit increased airway smooth muscle (ASM).
- Oxygen therapy and reactive oxygen species (ROS) are risk factors, but their interaction is unclear.
- Immature antioxidant defenses in premature infants may exacerbate lung injury.
Purpose of the Study:
- To investigate the direct effects of oxygen partial pressure (Po2) and ROS on fetal human ASM cell proliferation.
- To elucidate the relationship between Po2, mitogens, and ROS generation in ASM cells.
- To determine the role of ROS in mediating ASM proliferation under varying oxygen conditions.
Main Methods:
- Cultured fetal human ASM cells were exposed to varying Po2 levels and mitogens.
- ROS generation was measured using dichlorodihydrofluorescein oxidation.
- Cell proliferation was assessed by DNA synthesis assays.
- Effects of hydrogen peroxide (H2O2) and antioxidants (GSH, N-acetylcysteine) were evaluated.
Main Results:
- A bell-shaped relationship was observed between Po2 and mitogen-induced ASM cell DNA synthesis, peaking at 10-kPa Po2.
- Mitogens increased ROS generation, which was potentiated at lower Po2 levels.
- H2O2 mimicked Po2 effects on proliferation, while antioxidants inhibited it.
Conclusions:
- Elevated Po2 modulates fetal ASM cell proliferation in the presence of growth factors.
- ROS generation plays a significant role in mediating this Po2-induced ASM proliferation.
- Findings suggest a mechanism linking oxygen exposure, ROS, and airway remodeling in neonatal lung disease.
Abstract:
Increased airway smooth muscle (ASM) content is characteristic of infants with chronic lung disease of prematurity/bronchopulmonary dysplasia. Oxygen therapy, reactive oxygen species (ROS), and immature antioxidant defenses are major risk factors in chronic lung disease of prematurity/bronchopulmonary dysplasia, but their interrelationship is unclear. The direct effects of raised Po2 and modulation of ROS were examined on proliferation of cultured fetal human ASM cells. A bell-shaped relationship was found between Po2 and DNA synthesis induced by fetal bovine serum, platelet-derived growth factor, and basic fibroblastic growth factor, with peak responses occurring at 10-kPa Po2. Changes in DNA synthesis by Po2 did not occur in the absence of mitogen. ROS generation, estimated by dichlorodihydrofluorescein oxidation, was increased by mitogens but was unaffected by nonmitogens (bradykinin, histamine). There was an inverse relationship between ROS generation and Po2, and mitogen-induced ROS generation was substantially potentiated as the Po2 fell. H2O2 mimicked the effect of Po2 on fetal bovine serum-stimulated proliferation, whereas treatment with antioxidants (GSH, N-acetylcysteine) reduced it. These data demonstrate that increases in Po2 above levels found in utero modulate proliferation of fetal ASM cells but only in the presence of growth factors. They also strongly suggest that, under these conditions, proliferation is mediated in part by generation of ROS.
