Pulmonary di-and-triacylglycerols during the perinatal development of the rat

Tordet, C.; Marin, L.; Dameron, F

doi:10.1007/bf01959845

Cited by 33 publications

(34 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This pattern is consistent with the observation that alveolarization is delayed in Thy-1 2/2 mice (25). However, our findings differ from those in previous reports that indicate an earlier appearance of the pulmonary lipofibroblast (38,39), suggesting that the Thy-1 (1) lipofibroblast represents a distinct cell population. This assertion is supported by two observations.…”

Section: Discussioncontrasting

confidence: 99%

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Varisco

Ambalavanan

Whitsett

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Thy-1 is a glycosylphosphytidylinositol-linked cell-surface glycoprotein present on a subset of lung fibroblasts, which plays an important role in postnatal alveolarization. In the present study, we define the role of Thy-1 in pulmonary lipofibroblast differentiation and in the regulation of lipid homeostasis via peroxisome proliferator-activated receptor-g (PPARg). Thy-1 was associated with interstitial cells containing lipid droplets in vivo. The transfection of Thy-1 into Thy-1 (2) fibroblasts increased triglyceride content, fatty-acid uptake, and the expression of the lipofibroblast marker adipocyte differentiationrelated protein. Thy-1 (1) fibroblasts exhibited 2.4-fold higher PPARg activity, and the inhibition or activation of PPARg reduced and increased triglyceride content, respectively. Thy-1 (2) fibroblasts were not responsive to either of the PPARg agonists ciglitazone or prostaglandin J 2 , supporting the importance of Thy-1 in signaling via PPARg. Thy-1 (1) fibroblasts expressed significantly higher concentrations of fatty-acid transporter protein-3 mRNA, and demonstrated higher rates of fatty-acid uptake and increased triglyceride content. The inhibition of fatty-acid transporter protein function reduced Thy-1 (1) fibroblast lipid content. The expression of Thy-1 in C57BL/6 lung fibroblasts increased during the neonatal period, coinciding with the onset of alveolarization. Thy-1 promoted lipofibroblast differentiation via the expression of PPARg, stimulated lipid accumulation via fatty-acid esterification, and enhanced the fatty-acid uptake mediated by fattyacid transporter proteins. Thy-1 is important in the regulation of lipofibroblast differentiation in the developing lung.Keywords: Thy-1; lipofibroblast; PPARg; lipid metabolismBeginning at 35 weeks after conception and continuing for up to 8 years after birth, the alveolar stage of lung development is marked by the sequential division of larger airspaces into smaller ones by secondary alveolar septa (1, 2). From term birth until adulthood, the 5-fold increase in the number of alveoli and the 20-fold increase in alveolar surface area are critical in meeting the increasing oxygenation and ventilation needs of human growth and activity (2, 3). Premature birth, exposure to high concentrations of inspired oxygen, and mechanical ventilation lead to impaired alveolar development and chronic lung disease (4). The impaired lung function of chronic lung disease results in significant morbidity, mortality, and healthcare costs from early life through adulthood (5-8). Understanding how the different tissues of the lung behave during normal and impaired alveolar development is a key first step toward restoring alveolarization and attenuating the burden of respiratory disease after premature birth.Pulmonary lipofibroblasts comprise an incompletely characterized population of lipid-containing interstitial cells that play an important role in alveolarization. Hyperoxia, hypoxia, and nicotine exposure stimulate lipofibroblasts to myofibroblast differentiation a...

show abstract

Section: Discussioncontrasting

confidence: 99%

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Varisco

Ambalavanan

Whitsett

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…The situation in the developing lung is unusual in that a large amount of surfactant has to be produced within a short period of time. Lipid-laden lung fibroblasts (lipofibroblasts;McGowan & Torday 1997) are transiently observed during the perinatal period in the developing lung (Maksvytis et al 1981, Tordet et al 1981 where they are involved in lipid storage for surfactant production by PTII cells (Nunez & Torday 1995. In fact, triglyceride uptake by fibroblasts increases nine fold in the fetal rat lung between GDs 17 and 21.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex difference in surfactant lipids

Provost¹,

Boucher²,

Tremblay³

2008

Journal of Endocrinology

View full text Add to dashboard Cite

A sex difference in surfactant lipids is associated with a higher incidence of respiratory distress syndrome for males in cases of preterm birth. In animal models, the sex difference in surfactant lipids was shown to be androgen receptordependent. This report examines expression of apolipoprotein (apo)A-I, apoA-II, apoC-II, apoE, apoH, and lipoprotein lipase (LPL) by quantitative real-time PCR in pools of male and female fetal lung tissues from various mouse litters from gestation day (GD) 15 . 5 to 18 . 5, and in various adult tissues.Although the expression profiles of ApoA-I, ApoA-II, ApoC-II, and ApoH are complex, these genes are co-regulated and they all present a sex difference (PZ0 . 0896, 0 . 0896, 0 . 0195, and 0 . 0607 respectively) with higher expression for females for several litters. Pulmonary expression of apoA-I, apoA-II, and apoH were specific to the developing lung. ApoE and LPL mRNAs showed a significant increase from GD 17 . 5 to 18 . 5. An increase in apoA-I-, apoA-II-, apoC-II-, and apoHmRNA accumulation was observed from GD 16 . 5 to 17 . 5 in correlation with the emergence of mature type II pneumonocytes. These four apolipoprotein genes are co-regulated with type 2 and 5 17b-hydroxysteroid dehydrogenases, which are respectively involved in inactivation and synthesis of androgens. Finally, apoC-II was detected by immunohistochemistry in epithelial cells of the distal epithelium. Positive signals looking like secretory granules were located near the basal membrane. Our results are compatible with a role for apolipoproteins in lipid metabolism and transport in the developing lung in association with the sex difference in surfactant lipid synthesis.

show abstract

“…They also contain retinoic acids that are essential for the promotion of postnatal alveolar septation, a crucial process that increases bloodgas exchange surface (Simon and Mariani, 2007). LIFs are detected in the embryonic rat lung starting at embryonic day (E) 16; thereafter their numbers increase, peaking during the second postnatal week, when alveologenesis is at its peak (Tordet et al, 1981). Although LIFs have been studied in postnatal lungs, their exact cellular origin and mechanism of differentiation remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the involvement of Fibroblast Growth Factor 10 in lipofibroblast formation during embryonic lung development

et al. 2015

View full text Add to dashboard Cite

Lipid-containing alveolar interstitial fibroblasts (lipofibroblasts) are increasingly recognized as an important component of the epithelial stem cell niche in the rodent lung. Although lipofibroblasts were initially believed merely to assist type 2 alveolar epithelial cells in surfactant production during neonatal life, recent evidence suggests that these cells are indispensable for survival and growth of epithelial stem cells during adulthood. Despite increasing interest in lipofibroblast biology, little is known about their cellular origin or the molecular pathways controlling their formation during embryonic development. Here, we show that a population of lipid-droplet-containing stromal cells emerges in the developing mouse lung between E15.5 and E16.5. This is accompanied by significant upregulation, in the lung mesenchyme, of peroxisome proliferator-activated receptor gamma (master switch of lipogenesis), adipose differentiation-related protein (marker of mature lipofibroblasts) and fibroblast growth factor 10 (previously shown to identify a subpopulation of lipofibroblast progenitors). We also demonstrate that although only a subpopulation of total embryonic lipofibroblasts derives from Fgf10 + progenitor cells, in vivo knockdown of Fgfr2b ligand activity and reduction in Fgf10 expression lead to global reduction in the expression levels of lipofibroblast markers at E18.5. Constitutive Fgfr1b knockouts and mutants with conditional partial inactivation of Fgfr2b in the lung mesenchyme reveal the involvement of both receptors in lipofibroblast formation and suggest a possible compensation between the two receptors. We also provide data from human fetal lungs to demonstrate the relevance of our discoveries to humans. Our results reveal an essential role for Fgf10 signaling in the formation of lipofibroblasts during late lung development.

show abstract

Pulmonary di-and-triacylglycerols during the perinatal development of the rat

Cited by 33 publications

References 9 publications

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Thy-1 Signals through PPARγ to Promote Lipofibroblast Differentiation in the Developing Lung

Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex difference in surfactant lipids

Evidence for the involvement of Fibroblast Growth Factor 10 in lipofibroblast formation during embryonic lung development

Contact Info

Product

Resources

About