Oxygen dose responsiveness of human fetal airway smooth muscle cells

Hartman, William R.; Smelter, Dan F.; Sathish, Venkatachalem; Karass, Michael; Kim, Sunchin; Aravamudan, Bharathi; Thompson, Michael A.; Amrani, Yassine; Pandya, Hitesh; Martin, Richard J.; Prakash, Y. S.; Pabelick, Christina M.

doi:10.1152/ajplung.00037.2012

Cited by 78 publications

(104 citation statements)

References 60 publications

(24 reference statements)

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“…The increased Ca 2ϩ response in fetal human airway smooth muscle cells in hyperoxia-exposed cells is in line with previous data demonstrating a concentration-dependent increased proliferative response under mild to moderate hyperoxia (30 -50%) and hypoxia, whereas proliferation was reduced under high oxygen levels in these cells (60 -90%; see Ref. 18). These complimentary proliferative responses to moderate and high oxygen levels were recently confirmed in neonatal mice in which exposure to hyperoxia increased thickness of the airway smooth muscle layer, with a more severe response under moderate hyperoxia (40%) compared with high oxygen levels (70%; see Refs.…”

Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthsupporting

confidence: 92%

“…In this issue of Am J Physiol Lung Cell Mol Physiol, Britt et al (10) investigated the interaction between hyperoxia and sGC on Ca 2ϩ responses in human fetal airway smooth muscle cells. Fetal human airway smooth muscle cells are substantially different from adult human airway smooth muscle cells in their proliferative and Ca 2ϩ -signaling characteristics and exhibit marked changes in the expression profile of contractile proteins, receptors, and Ca 2ϩ -signaling effectors (18). They demonstrated that, upon exposure to moderate hyperoxia, fetal human airway smooth muscle cells show an increased histamine-induced Ca 2ϩ response that could be blunted by sGC activators and stimulators in a protein kinase G-dependent way.…”

Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthmentioning

confidence: 99%

“…Fetal human airway smooth muscle cells are not only different from adult human airway smooth muscle cells in their proliferative, Ca 2ϩ -signaling, and contractile characteristics (18), but these cells also respond to cigarette smoke extract with increased proliferation and extracellular matrix protein expression (41). This is of clear relevance to the development of asthma, since fetal exposure to maternal smoking increases asthma susceptibility and the development of airway smooth muscle mass (9).…”

Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease

Wagenaar

Hiemstra

Gosens

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Wagenaar GT, Hiemstra PS, Gosens R. Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease. Am J Physiol Lung Cell Mol Physiol 309: L1037-L1040, 2015. First published October 2, 2015; doi:10.1152/ajplung.00333.2015.-Supplemental oxygen after premature birth results in aberrant airway, alveolar, and pulmonary vascular development with an increased risk for bronchopulmonary dysplasia, and development of wheeze and asthma, pulmonary hypertension, and chronic obstructive pulmonary disease in survivors. Although stimulation of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway has significant beneficial effects on disease development in animal models, so far this could not be translated to the clinic. Oxidative stress reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in inactivation or degradation of sGC. Reduced sGC activity and/or expression is associated with pathology due to premature birth, oxidative stress-induced lung injury, including impaired alveolar maturation, smooth muscle cell (SMC) proliferation and contraction, impaired airway relaxation and vasodilation, inflammation, pulmonary hypertension, right ventricular hypertrophy, and an aggravated response toward hyperoxia-induced neonatal lung injury. Recently, Britt et al. (10) demonstrated that histamine-induced Ca 2ϩ responses were significantly elevated in hyperoxia-exposed fetal human airway SMCs compared with normoxic controls and that this hyperoxia-induced increase in the response was strongly reduced by NO-independent stimulation and activation of sGC. These recent studies highlight the therapeutic potential of sGC modulators in the treatment of preterm infants for respiratory distress with supplemental oxygen. Such treatment is aimed at improving aberrant alveolar and vascular development of the neonatal lung and preventing the development of wheezing and asthma in survivors of premature birth. In addition, these studies highlight the suitability of fetal human airway SMCs as a translational model for pathological airway changes in the neonate.airway remodeling, calcium response; fetal human airway smooth muscle cells; hyperoxia; oxidative stress; nitric oxide; soluble guanylate cyclase; guanosine 3=, 5=-cyclic monophosphate TREATMENT OF RESPIRATORY DISTRESS after premature birth with supplemental oxygen may interfere with the development of the immature lung, resulting in aberrant airway, alveolar, and vascular development. Survivors of premature birth are at risk for developing pulmonary arterial hypertension, recurrent wheeze and asthma, and chronic obstructive pulmonary disease (COPD) at relatively young ages (3,6,17,21,34). The underlying pathology has a multifactorial etiology, and the NO-soluble guanylate cyclase (sGC)-cGMP pathway is involved in many factors that contribute to it. Nitric oxide (NO) is a key signaling molecule in many biological and physiological processes, regulating cell growth, differentiation, proliferation, smooth muscle r...

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Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthsupporting

confidence: 92%

Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthmentioning

confidence: 99%

Section: Impact Of Neonatal Lung Disease and Oxygen Treatment On Asthmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease

Wagenaar

Hiemstra

Gosens

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…We have previously documented that exposure to Ͼ95% oxygen upregulates epithelial arginase in neonatal rat pups, which would be expected to increase lung collagen content and potentially restrict airway constriction (1). Furthermore, we have shown that levels of supplemental oxygen Ͼ60% cause apoptosis in human fetal ASM cells in contrast to the ASM proliferation observed at lower levels of oxygen exposure (6). This is consistent with the inhibition of apoptosis observed in lung cells of neonatal rats exposed to 60% compared with 95% oxygen (23).…”

mentioning

confidence: 92%

Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway

Wang

Jafri

Martin

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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MacFarlane PM. Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway. Am J Physiol Lung Cell Mol Physiol 307: L295-L301, 2014. First published June 20, 2014 doi:10.1152/ajplung.00208.2013.-Wheezing is a major long-term respiratory morbidity in preterm infants with and without bronchopulmonary dysplasia. We hypothesized that mild vs. severe hyperoxic exposure in neonatal mice differentially affects airway smooth muscle hypertrophy and resultant airway reactivity. Newborn mice were exposed to 7 days of mild (40% oxygen) or severe (70% oxygen) hyperoxia vs. room air controls. Respiratory system resistance (Rrs), compliance (Crs), and airway reactivity were measured 14 days after oxygen exposure ended under ketamine/ xylazine anesthesia. Baseline Rrs increased and Crs decreased in both treatment groups. Methacholine challenge dose dependently increased Rrs and decreased Crs in 40% oxygen-exposed mice, whereas Rrs and Crs responses were similar between 70% oxygen-exposed and normoxic controls. Airway smooth muscle thickness was increased in 40%-but not 70%-exposed mice, whereas collagen increased and both alveolar number and radial alveolar counts decreased after 40% and 70% oxygen. These data indicate that severity of hyperoxia may differentially affect structural and functional changes in the developing mouse airway that contribute to longer-term hyperreactivity. These findings may be important to our understanding of the complex role of neonatal supplemental oxygen therapy in postnatal development of airway responsiveness.

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“…In turn, these ECM components are themselves modulated by diseases such as asthma, COPD, and pulmonary fibrosis (i.e., many of the same diseases that are indications for lung transplantation). Factors such as altered oxygen levels (2,16,69,110,120,157,210,221,226), environmental influences (23,211), and inflammatory and profibrotic mediators (3,4,9,30,154,209,229) can modulate the expression of collagens, fibronectin, elastin. and other important lung ECM components.…”

Section: Materials Matrix and Mechanobiologymentioning

confidence: 99%