Self-differentiation of human fetal lung organ culture: The role of prostaglandins PGE2 and PGF2α

Hume, Robert; Kelly, Rodney W.; Cossar, David; Giles, M.; Hallas, Anne; Gourlay, Margaret; Bell, Jeanne E.

doi:10.1016/0014-4827(91)90138-k

Cited by 23 publications

(10 citation statements)

References 27 publications

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“…However, there is no information regarding how stretch stimulates surfactant phospholipid synthesis. Developing TII cell surfactant phospholipid synthesis is controlled by a wide variety of growth factors (13), cytokines (41), and eicosanoids (10), which mediate the paracrine regulation of fetal lung development. Among these, prostaglandin E 2 (PGE 2 ) and parathyroid hormone-related protein (PTHrP) production by TII cells is stimulated by stretch, and each can stimulate surfactant phospholipid production (25,36).…”

mentioning

confidence: 99%

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Torday

Rehan²

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

127

146

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Torday, J. S., and V. K. Rehan. Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin. Am J Physiol Lung Cell Mol Physiol 283: L130-L135, 2002. First published February 22, 2002; 10.1152/ajplung.00380.2001.-Intrauterine lung development, culminating in physiological pulmonary surfactant production by epithelial type II (TII) cells, is driven by fluid distension through unknown mechanisms. Differentiation of alveolar epithelial and mesenchymal cells is mediated by soluble factors like parathyroid hormone-related protein (PTHrP), a stretch-sensitive TII cell product. PTHrP stimulates pulmonary surfactant production by a paracrine feedback loop mediated by leptin, a soluble product of the mature lipofibroblast (LF). When LFs and TIIs are stretched in coculture, there is a fivefold increase in surfactant phospholipid synthesis that can be "neutralized" by inhibitors of PTHrP or leptin, implicating a paracrine feedback loop in this mechanism. Stretching LFs stimulates PTHrP binding (2.5-fold) and downstream stimulation of triglyceride uptake quantitatively (15-25%) due to upregulation of adipose differentiation-related protein expression. Stretching TII cells increases leptin stimulation of their surfactant phospholipid synthesis threefold, suggesting that retrograde signaling by leptin to TII cells is also stretch sensitive. We conclude that the effect of stretch on alveolar LF and TII differentiation is coordinated by PTHrP, leptin, and their receptors.lipofibroblast; parathyroid hormone-related protein; leptin; adipose differentiation-related protein INTRAUTERINE LUNG DEVELOPMENT is driven by lung fluid secretion, which distends the alveolar acinus, forming a "bubblelike" template for its structure and function (2, 16). Stretch stimulates the growth and differentiation of both the epithelial and mesenchymal cells of the alveolar septal wall in preparation for air breathing at the time of birth. Of particular importance to the transition from intrauterine to extrauterine adaptation is the synthesis and secretion of pulmonary surfactant by alveolar type II cells. The surfactant reduces surface tension of the lung lining layer, preventing atelectasis of the air-filled lung. The surfactant is a complex of both proteins and phospholipids, the latter being responsible for the lowering of surface tension.It has previously been shown that stretching stimulates the growth of cultured mixed lung cells (15) and the secretion of pulmonary surfactant phospholipid by epithelial type II (TII) cells (38). It has subsequently been shown that stretch increases the expression of surfactant proteins (27). However, there is no information regarding how stretch stimulates surfactant phospholipid synthesis. Developing TII cell surfactant phospholipid synthesis is controlled by a wide variety of growth factors (13), cytokines (41), and eicosanoids (10), which mediate the paracrine regulation of fetal lung development. Among these, prostaglandin E 2 (PGE 2 ) and parathyroid hormone-related p...

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mentioning

confidence: 99%

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Torday

Rehan²

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

127

146

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“…This suggests inhibitory mechanisms prevail in utero, delaying human fetal lung development, perhaps as a fully functioning gas exchange system is not required. Prostaglandins are important during in vitro human fetal lung autodifferentiation with addition of PGE 2 , but not PGF 2α , accelerating this process (Hume et al 1991). Indomethacin, which inhibits prostaglandin H synthase activity, arrests this accelerated differentiation but this can be reversed by further addition of PGE 2 (Hume et al 1991).…”

Section: Introductionmentioning

confidence: 98%

Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase

Conner

Kelly

Hume

2001

Histochem Cell Biol

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Specialisation of the respiratory portion of human fetal lung commences around 20-24 weeks gestation. In contrast, human fetal lung in vitro has the capacity to self-differentiate from 12 weeks gestation when grown in media devoid of growth factors or hormones, suggesting activation of autocrine or paracrine factors in vitro, or removal of the fetus from in utero inhibitory mechanisms. Prostaglandins play a key role during in vitro human fetal lung development and are synthesised by prostaglandin H synthase-1 (PGHS-1) and inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH) with formation of inactive 13,14-dihydro-15-keto-prostaglandins. We have used quantitative immunohistochemistry to determine expression and localisation of PGHS-1, PGDH, PGE2 and 13,14-dihydro-15-keto-PGE2 (PGEM) in human fetal lung with in situ hybridisation to localise PGHS-1 and PGDH mRNA. For the catabolic enzyme PGDH, amounts of mRNA, protein and enzyme product PGEM are increased within epithelium of distal as compared to more proximal airways. For PGHS-1, comparable amounts of mRNA, protein and enzyme product PGE2 are found in proximal and distal lung epithelium. Catabolism by PGDH is a sensitive mechanism for regulating bioavailability of prostaglandins and we propose that active catabolism of prostaglandins within human fetal lung epithelium is an inhibitory mechanism retarding epithelial differentiation in utero.

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“…These changes occur in sera-free media in the absence of exogenous hormones or growth factors, suggesting the presence of endogenous regulatory factors. Prostaglandins are produced in substantial amounts by human fetal lung in culture (Hume et al 1991), possibly as a result of oxidative and mechanical stresses . Tndomethacin inhibits endogenous prostaglandin production, the process of accelerated self-development and the spontaneous induction of SP-A gene expression.…”

Section: Prostaglandinsmentioning

confidence: 99%

“…Tndomethacin inhibits endogenous prostaglandin production, the process of accelerated self-development and the spontaneous induction of SP-A gene expression. Addition of exogenous prostaglandin E2 reverses the indomethacin inhibition on morphological development and SP-A expression (Accaregui et al 1990;Ballard et al 1991;Hume et al 1991).…”

Section: Prostaglandinsmentioning

confidence: 99%

Lung maturation

Hume¹,

Conner²,

Gilmour³

1996

Proc. Nutr. Soc.

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Self-differentiation of human fetal lung organ culture: The role of prostaglandins PGE2 and PGF2α

Cited by 23 publications

References 27 publications

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin

Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase

Lung maturation

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