Influence of Oxygen Tension on Somatomedin Activity in Vitro

Dehnel, J.M.; Hamblen, David L.

doi:10.1677/joe.0.0720361

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Hypoxia enhances the ability of chondrocytes to incorporate thymidine in response to IGF-I (Dehnel and Hamblen, 1977). Our laboratory has recently shown that PMA pretreatment allows PA SMC to proliferate in response to hypoxia (Dempsey et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Insulin‐Like growth factor I and protein kinase C activation stimulate pulmonary artery smooth muscle cell proliferation through separate but synergistic pathways

Dempsey

Stenmark

McMurtry

et al. 1990

Journal Cellular Physiology

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Smooth muscle cell (SMC) hyperplasia is an important component of vascular remodeling in chronic hypoxic pulmonary hypertension. The mechanisms underlying SMC proliferation in the remodeling process are poorly understood, but may involve insulin-like growth factor I (IGF-I). This study investigates the potential proliferative effects of IGF-I on SMC cultured from the pulmonary arteries (PA) of neonatal calves. We hypothesized that IGF-I stimulates PA SMC proliferation through a protein kinase C (PKC)-independent pathway, but that PKC activation would augment this proliferative response. Incorporation of 3H-thymidine was used as an index of cellular proliferation, and was correlated with subsequent changes in cell counts. Under serum-free conditions, IGF-I (100 ng/ml) induced a 6-fold increase in thymidine incorporation by quiescent PA SMC. This stimulation was not blocked by dihydrosphingosine, an inhibitor of PKC activation. Phorbol myristate acetate (PMA) (1 nM), a membrane-permeable PKC activator, induced a 12-fold increase in thymidine incorporation which was 70% inhibited by dihydrosphingosine. Co-incubation with IGF-I and PMA caused a 60-fold increase in thymidine incorporation, which was 30% inhibited by dihydrosphingosine. This synergistic increase in thymidine incorporation was associated with a subsequent significant increase in cell number. PKC-downregulated cells (1,000 nM PMA x 30 hr) proliferated in response to IGF-I but not PMA, and did not demonstrate synergism with the combination of IGF-I and PMA. The threshold concentrations of IGF-I and PMA for synergism were approximately 1 ng/ml and 1 pM, respectively. We conclude that IGF-I stimulates neonatal PA SMC proliferation via a PKC-independent pathway, and that trace amounts of PKC activators are capable of synergistically augmenting this response. We speculate that the synergistic stimulation of SMC proliferation by IGF-I and PKC activators may play an important role in hypertensive pulmonary vascular remodeling.

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Section: Discussionmentioning

confidence: 99%

Insulin‐Like growth factor I and protein kinase C activation stimulate pulmonary artery smooth muscle cell proliferation through separate but synergistic pathways

Dempsey

Stenmark

McMurtry

et al. 1990

Journal Cellular Physiology

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“…The more rapid proliferation of fibroblasts in hypoxic regions of tissue during wound healing (43) may be reflected in the more rapid growth of these cells at oxygen tensions of 20 to 40 mm Hg in vitro (10,11). Chondrocytes proliferate more rapidly in the relatively avascular core of the developing limb bud (44) and in avascular growing mature cartilage, as well as at lower oxygen tensions in vitro (12). Cardiac enlargement in hypoxic fetuses (45) may result, at least in part, from more rapid proliferation of embryonic myocardial cells at decreased oxygen tensions (13).…”

Section: Discussionmentioning

confidence: 99%

“…Proliferation could be accelerated by hypoxia itself, as has been reported for fibroblasts (10, II), chondrocytes (12), and embryonic myocardial cells (13). We have examined the effects of oxygen tension on proliferation of SMC cultured from the pulmonary arteries of near-term bovine fetuses.…”

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confidence: 81%

Hypoxia Inhibits Proliferation of Fetal Pulmonary Arterial Smooth Muscle Cells in Vitro

et al. 1986

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ABSTRACT. Normal pulmonary arterial development in the relatively hypoxic intrauterine environment and pulmonary arterial remodeling in hypoxic infants include extension of the smooth muscle layer into normally nonmuscular arteries and thickening of the arterial media in the muscular arteries. These changes require proliferation of immature smooth muscle cells or differentiation of smooth muscle cell precursors. Because the mechanisms that regulate these processes have not been clearly defined, we asked whether decreased oxygen tensions could promote either hyperplasia or hypertrophy of smooth muscle cell precursors in vitro. We have studied cells that proliferate and migrate out of explants from the media of the pulmonary arteries of near-term bovine fetuses, because these cells are representative of those that are involved in normal arterial development and possibly also in arterial remodeling. Decreases in oxygen tension within and below the physiologic range do not cause hyperplasia or hypertrophy of these cells. Instead, cell proliferation decreased at oxygen tensions below 60 mm Hg. The effects of hypoxia on proliferation of aortic and pulmonary arterial smooth muscle cells were identical, but effects on proliferation of dermal fibroblasts and endothelial cells were smaller in magnitude and evident only at lower oxygen tensions. These findings suggest that hypoxia does not act directly on smooth muscle cells to produce increased quantities of these cells in the pulmonary arteries during normal prenatal development or during remodeling of the pulmonary arteries of the hypoxic neonate, implying that other factors mediate these phenomena. (Pediatr Res 20: 966-972, 1986) man infants (5-7). The proximal muscular arteries are remodeled by thickening of the tunica media, which may be caused by hypertrophy of medial smooth muscle cells (6), increased abundance of extracellular matrix (3), proliferation of SMC, and/or differentiation of their precursors (I). The peripheral nonmuscular and partially muscular arteries are remodeled by appearance of new smooth muscle in those vessels (I, 2, 4), a process that requires proliferation of SMC or their precursors. Proliferation and peripheral extension of the SMC in the media of the pulmonary arteries is also prominent in normal prenatal development (8, 9), and it has been suggested that the relative hypoxia of the intrauterine environment may be an important stimulus for this process (9).The mechanisms that regulate proliferation and differentiation of SMC or their precursors in the fetus and newborn are unknown. Proliferation could be accelerated by hypoxia itself, as has been reported for fibroblasts (10, II), chondrocytes (12), and embryonic myocardial cells (13). We have examined the effects of oxygen tension on proliferation of SMC cultured from the pulmonary arteries of near-term bovine fetuses. At oxygen tensions within and below the physiologic range, lower oxygen tensions were associated with reduced proliferation of these cells, and cellular hypertrophy was ...

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“…Ashton & Francis (1977) and Corvol et al (1978) developed a bioassay for serum somatomedins using rabbit chon¬ drocytes and Dehnel & Hamblen (1977) used rat epiphyseal chondrocytes. Yasumoto et al (1980) reported that the chondrocytes obtained from 13 day old chick embryos could easily be cultured in the floating state, retaining the phenotypic proper¬ ties as chondrocytes.…”

mentioning

confidence: 99%

Serum somatomedin activity assayed by the enhancement of proteoglycan sulphation using chick embryo chondrocytes in normal children at various ages and childen of short stature

Maesaka

Yokoya

Tachibana

et al. 1982

Acta Endocrinologica

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It was possible to obtain a sufficient amount of homogeneous chondrocytes from 13-day old chick embryo-sterna in an 8-day suspension culture. Serum somatomedin (SM) activity was measured on the basis of the ability of serum to stimulate labelled sulphate uptake in these chondrocytes. Somatomedin A and multiplication stimulating activity (MSA) stimulated the sulphation in this assay. Serum SM activity in term cord sera and newborn sera was lower than that in normal adults.Serum SM activity in early infants increased rapidly and attained the levels of that in normal adults within 1 month following birth. Serum SM activity in infants (1 month \p=m-\2 years) and pubertal children(10\p=n-\16 years), when the annual height increment is greatest, was higher than that in normal adults.Serum SM activity in children with constitutinal dwarfism aged 6\p=n-\10 years and over 10 years was normal and lower, respectively, compared to that in age-matched controls.

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Influence of Oxygen Tension on Somatomedin Activity in Vitro

Cited by 7 publications

References 19 publications

Insulin‐Like growth factor I and protein kinase C activation stimulate pulmonary artery smooth muscle cell proliferation through separate but synergistic pathways

Insulin‐Like growth factor I and protein kinase C activation stimulate pulmonary artery smooth muscle cell proliferation through separate but synergistic pathways

Hypoxia Inhibits Proliferation of Fetal Pulmonary Arterial Smooth Muscle Cells in Vitro

Serum somatomedin activity assayed by the enhancement of proteoglycan sulphation using chick embryo chondrocytes in normal children at various ages and childen of short stature

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