Changes in alveolar septal border lengths  with postnatal lung growth

Wood, Jonathan P.; Kolassa, John E.; McBride, John T.

doi:10.1152/ajplung.1998.275.6.l1157

Cited by 8 publications

(14 citation statements)

References 24 publications

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“…A new interalveolar septal bud arises as a double capillary layer with elastin localized at the tip. Tension on elastin fibers causes lengthening of the new septa (Figure 2) (Oldmixon, et al, 1988) (Weibel, 2009, Wood, et al, 1998). Myofibroblasts exhibit asymmetric localization of phosphorylated epidermal growth factor receptor (phospho-EGFR), which directs cell migration.…”

Section: Mechanical Signals In Lung Developmentmentioning

confidence: 99%

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Comparative analysis of the mechanical signals in lung development and compensatory growth

Hsia

2017

Cell Tissue Res

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This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax, and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships, and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling, may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences, and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.

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Section: Mechanical Signals In Lung Developmentmentioning

confidence: 99%

“…Elastic fibers (stained black) support the free tips of the alveolar septa (right). Adapted from (Oldmixon, et al, 1989, Weibel, 2009, Wood, et al, 1998). …”

Section: Figurementioning

confidence: 99%

Comparative analysis of the mechanical signals in lung development and compensatory growth

Hsia

2017

Cell Tissue Res

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“…Alveolar walls have been likened to tents supported by ropes (elastic fibers) and poles, whose lengths and tension largely determine the shape of the tent (148). Mechanical stresses provide signals for the orientation and differentiation of alveolar myofibroblasts as well as directional organization of a complex elastic fiber network.…”

Section: Extracellular Matrix and Elastic Fibersmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

145

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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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“…This exponential increase in gas-exchange capacity is essential to meeting the bioenergetic needs of ex utero growth and development. Formation of a low-compliance elastin band at the leading edge of a growing secondary alveolar septal ridge likely plays critical mechano-developmental role in alveolar septation [3-6]. …”

Section: Introductionmentioning

confidence: 99%

JNK suppresses pulmonary fibroblast elastogenesis during alveolar development

et al. 2014

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BackgroundThe formation of discrete elastin bands at the tips of secondary alveolar septa is important for normal alveolar development, but the mechanisms regulating the lung elastogenic program are incompletely understood. JNK suppress elastin synthesis in the aorta and is important in a host of developmental processes. We sought to determine whether JNK suppresses pulmonary fibroblast elastogenesis during lung development.MethodsAlveolar size, elastin content, and mRNA of elastin-associated genes were quantitated in wild type and JNK-deficient mouse lungs, and expression profiles were validated in primary lung fibroblasts. Tropoelastin protein was quantitated by Western blot. Changes in lung JNK activity throughout development were quantitated, and pJNK was localized by confocal imaging and lineage tracing.ResultsBy morphometry, alveolar diameters were increased by 7% and lung elastin content increased 2-fold in JNK-deficient mouse lungs compared to wild type. By Western blot, tropoelastin protein was increased 5-fold in JNK-deficient lungs. Postnatal day 14 (PND14) lung JNK activity was 11-fold higher and pJNK:JNK ratio 6-fold higher compared to PN 8 week lung. Lung tropoelastin, emilin-1, fibrillin-1, fibulin-5, and lysyl oxidase mRNAs inversely correlated with lung JNK activity during alveolar development. Phosphorylated JNK localized to pulmonary lipofibroblasts. PND14 JNK-deficient mouse lungs contained 7-fold more tropoelastin, 2,000-fold more emilin-1, 800-fold more fibrillin-1, and 60-fold more fibulin-5 than PND14 wild type lungs. Primarily lung fibroblasts from wild type and JNK-deficient mice showed similar differences in elastogenic mRNAs.ConclusionsJNK suppresses fibroblast elastogenesis during the alveolar stage of lung development.

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Changes in alveolar septal border lengths with postnatal lung growth

Cited by 8 publications

References 24 publications

Comparative analysis of the mechanical signals in lung development and compensatory growth

Comparative analysis of the mechanical signals in lung development and compensatory growth

Mechanisms and Limits of Induced Postnatal Lung Growth

JNK suppresses pulmonary fibroblast elastogenesis during alveolar development

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