Influence of maternal pneumonectomy of fetal lung growth

Faridy, Edmund E.; Sanii, M.R.; Thliveris, James A.

doi:10.1016/0034-5687(88)90006-0

Cited by 13 publications

(4 citation statements)

References 14 publications

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“…In pregnant rats, pneumonectomy increases DNA content in the fetal lung (268). Assuming that the maternal blood is not hypoxemic, data suggest that soluble growth factors released into maternal circulation are capable of crossing the placenta to stimulate fetal lung growth.…”

Section: Nonmechanical Signals and Mediatorsmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

140

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Abnormal DevelopmentClinical syndromes. Syndromes that alter expression of growth factors, cytokines, transcription factors, or extracellular matrix (ECM) proteins provide models to explore mechanisms that control alveolar development. Signals that regulate the saccularto-alveolar morphologic transition are poorly understood, but disrupting lung septation during this transition impairs alveolar formation, resulting in a loss of alveolar surface area (20, 21). There are several syndromes of abnormal lung alveolarization in humans. Trisomy 21 (Down syndrome) is associated with reduced lung volumes, alveolar surface area, fewer alveoli, defective elastin deposition, and vascular abnormalities (22, 23). Leprechaunism, caused by a defect of the insulin/insulin-like growth factor-I receptor, is associated with reduced lung surface areas as well as fewer and larger alveoli (24). Oligohydramnios (25), congenital diaphragmatic hernia (CDH) (26), and intrathoracic mass lesions are all associated with pulmonary hypoplasia caused by the lack of interplay between thoracic expansion and stretch imposed on the lung. Lung hypoplasia in CDH is not just a consequence of mechanical lung compression caused by a hole in the diaphragm but also involves primary developmental defects (27). Prenatal tracheal occlusion markedly increases lung size in some fetuses with severe CDH; however, survival remains poor because of respiratory insufficiency and prematurity (28). After CDH repair, significant postnatal alveolar growth and vascular remodeling are seen (26); long-term survivors show lower lung volumes but normal airway function and exercise tolerance (29), suggesting the occurrence of "catch-up" lung growth once the underlying abnormalities are corrected.By far the most common cause of abnormal postnatal human lung development is bronchopulmonary dysplasia (BPD). Classically, BPD occurs in the preterm infant lung exposed to hyperoxia and mechanical ventilation (30-32), resulting in extensive alveolar fibroproliferation, bronchovascular smooth muscle hyperplasia, and inhibition of distal lung formation leading to longterm pulmonary dysfunction persisting into adolescence and adulthood. The advent of antenatal steroids, postnatal surfactant replacement, and improved intensive care has ushered in the "new BPD," which lacks the severe bronchovascular lesions and interstitial fibrosis but is characterized by abnormal lung development with simplified acinar structure, poorly formed secondary crests, dysmorphic alveolar capillaries, and blunted expression of angiogenic growth factors and their receptors (33-36). There is little information on the pathology of "new BPD" in infants who survive; it remains to be seen whether long-term "catch-up" lung growth occurs in these survivors.

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Section: Nonmechanical Signals and Mediatorsmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

140

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“…Although the young mice were virgins, all the older mice were retired breeders (purchased at 8 months of age) in this study. Since previous studies have established that an earlier pregnancy does not alter compensatory lung regrowth [22], it was assumed that aging was the major factor influencing cell behavior in this study. For surgery, mice were anesthetized by an intraperitoneal injection of ketamine (50-75 mg/kg) and xylazine (5 mg/kg), and they then received 2 mL of warmed normal saline and 100 mg/kg sodium ampicillin subcutaneously.…”

Section: Animals and Surgical Procedures Used For Lmsc Studiesmentioning

confidence: 99%

Age Dependence of Lung Mesenchymal Stromal Cell Dynamics Following Pneumonectomy

Paxson

Gruntman²,

Davis³

et al. 2013

Stem Cells and Development

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Aging is a critical determinant of regenerative capacity in many organ systems, but it remains unresolved in the lung. This study examines murine lung cell dynamics during age-dependent lung regeneration. Proliferation of lung progenitor cells (EpCAM neg /Sca-1 high lung mesenchymal stromal cells -LMSCs, EpCAM pos /Sca-1 low epithelial progenitor cells, proSP-C pos alveolar type II epithelial cells -AECII, and CD31 pos -endothelial cells) was tracked to day 3 or 7 after pneumonectomy (PNX) or SHAM surgery in 3, 9, and 17 month mice. In 3 month mice, post-PNX LMSC proliferation peaked early (3 days), with 50%-80% more BrdU-positive cells than the other cell types, which peaked later (4-7 days). In older mice (9 and 17 month), abundance and post-PNX proliferation of LMSCs at day 3 were reduced (40%-80%). In both young and old mice, LMSCs were isolated and compared phenotypically with whole lung non-LMSCs. Donor age had no qualitative effect on the phenotype (LMSC vs. non-LMSC), with increased expression of CD90/Thy1, CD105/Eng, CD106/Vcam, CD146/Mcam, and Pdgfra, and up-regulation of mRNA encoding Fap, Eln, Col1a1, Col3a1, Aldh1a3, Arhgef25, Dner, Fgfr1, and Midkine. However, compared with LMSCs isolated from young mice, LMSCs from older mice exhibited reduced mRNA expression of retinoic acid (Aldh1a3, Rbp4), Fgf/Wnt (Fgfr1, Sfrp1, Wnt2, and Ctnnb1), and elastogenesis (Col1a1, Eln, Fbn1, and Sdc2) pathway genes. Isolated LMSCs from older mice also demonstrated lower colony-forming units ( -67%), growth potential ( -60% by day 7), ALDH activity ( -49%), and telomerase activity ( -47%). Therefore, age is associated with declining proliferative potential and regenerative functions of LMSCs in the lung.

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“…Pregnant and non-pregnant rats undergo similar courses of compensatory lung growth; in contrast, fetal lung growth is enhanced in pregnant rats subjected to PNX [43]. This effect is specific to the lung, as increases in DNA content and tissue mass are not observed in fetal liver, kidneys or placenta [43]. These data suggest the presence of unidentified lung-specific growth factors in the circulation of pregnant PNX rats.…”

Section: Regulation Of Post-pnx Growthmentioning

confidence: 99%

Implications of post-pneumonectomy compensatory lung growth in pulmonary physiology and disease

Brown

Rannels

2001

Respir Res

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ADX = adrenalectomy; BHT = butylated hydroxytoluene; BW = body weight; GH = growth hormone; IGF = insulin-like growth factor; PNX = partial pneumonectomy; RLW = right lung weight; SHAM = sham pneumonectomy; TLW = total lung weight.Available online http://respiratory-research.com/content/2/6/340 IntroductionPartial pneumonectomy (PNX), the surgical removal of a lung lobe or lobes, substantially diminishes diffusion capacity by reducing the total number of alveoli and the associated vasculature available for gas exchange. The immediate challenge to a pneumonectomized animal is to maintain adequate gas exchange following resection of lung tissue. Physiological compensation for the loss of lung mass is achieved primarily through two mechanisms: enhancement of diffusion capacity in the remnant lung, and/or generation of new pulmonary gas exchange units.PNX elicits a number of anatomical changes within the thoracic cavity that augment the diffusion capacity of the remaining lobes. Ligation and surgical removal of one or more lobes directs the entire cardiac output into remaining lung tissue and creates an empty hemithorax that results in a shift of the mediastinum toward the vacated thoracic compartment [1,2]. In addition, increased space within the chest releases constraints on lung expansion imposed by the thoracic wall. Increased lung inflation on inspiration can then recruit alveoli that might have been incompletely ventilated prior to PNX. Likewise, increased pulmonary blood flow to the remaining tissue may contribute to tissue distension and enhance parenchymal perfusion. As a consequence of these post-surgical anatomical changes, adequate gas exchange can be re-established after PNX by exploiting the physiological reserves of diffusion capacity in the remaining lung tissue.A second adaptive response to PNX is compensatory growth of the remaining lobes. In a variety of mammalian species, PNX stimulates rapid compensatory lung growth, restoring normal mass, structure and function. Although post-PNX compensatory lung growth has been documented in rabbits [3], mice [4,5], ferrets [6,7] and dogs [8,9] AbstractIn a number of species, partial pneumonectomy initiates hormonally regulated compensatory growth of the remaining lung lobes that restores normal mass, structure and function. Compensation is qualitatively similar across species, but differs with gender, age and hormonal status. Although the biology of response is best characterized in rats, dogs have proven valuable in defining post-operative physiological adaptations. Most recently, mice were recognized to offer unique opportunities to explore the genetic basis of the response, as well as to evaluate associated detrimental effects of pathophysiological significance in animals exposed to carcinogens. The pneumonectomy model thus offers powerful insight concerning adaptive organ growth.

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Influence of maternal pneumonectomy of fetal lung growth

Cited by 13 publications

References 14 publications

Mechanisms and Limits of Induced Postnatal Lung Growth

Mechanisms and Limits of Induced Postnatal Lung Growth

Age Dependence of Lung Mesenchymal Stromal Cell Dynamics Following Pneumonectomy

Implications of post-pneumonectomy compensatory lung growth in pulmonary physiology and disease

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