Thyroid hormone affects distal airway formation during the late pseudoglandular period of mouse lung development

Volpe, MaryAnn V.; Nielsen, Heber C.; Archavachotikul, Kwanchai; Ciccone, Terrigi J; Chinoy, Mala R.

doi:10.1016/j.ymgme.2003.08.018

Cited by 8 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar doses were shown in other in vitro studies to affect the biochemical and structural development of the lung in late fetal and postnatal life. (11,19,25,26,51). Thus the dose effect of T 3 that we have observed in early lung development is comparable to previous studies in late lung development in which doses Ͻ1 nM had little or no effect and doses of 1-100 nM produced progressive changes in lung maturation, with a maximum effect at 10 nM (11,23,26).…”

Section: Discussionsupporting

confidence: 87%

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Archavachotikul

Ciccone

Chinoy

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Although thyroid hormone (T3) influences epithelial cell differentiation during late fetal lung development, its effects on early lung morphogenesis are unknown. We hypothesized that T3 would alter embryonic lung airway branching and temporal-spatial differentiation of the lung epithelium and mesenchyme. Gestational day 11.5 embryonic mouse lungs were cultured for 72 h in BGJb serum-free medium without or with added T 3 (0.2, 2.0, 10.0, or 100 nM). Evaluation of terminal bud counts showed a dose-and time-dependent decrease in branching morphogenesis. Cell proliferation was also significantly decreased with higher doses of T 3. Morphometric analysis of lung histology showed that T 3 caused a dose-dependent decrease in mesenchyme and increase in cuboidal epithelia and airway space. Immunocytochemistry showed that with T 3 treatment, Nkx2.1 and surfactant protein SP-C proteins became progressively localized to cuboidal epithelial cells and mesenchymal expression of Hoxb5 was reduced, a pattern resembling late fetal lung development. We conclude that exogenous T 3 treatment during early lung development accelerated epithelial and mesenchymal cell differentiation at the expense of premature reduction in new branch formation and lung growth. triiodothyronine; lung development; Nkx2.1; Hoxb5; surfactant protein-C DURING FETAL DEVELOPMENT, lung morphology and differentiation of the airway lining epithelium change with advancing gestation. In the mouse, lung morphogenesis starts at gestational day 9.5 (Gd 9.5) with the evagination of the lung primordium from the ventral foregut to form the prospective trachea and two lung buds followed by the dichotomous branching of each lung bud through the process of branching morphogenesis. Differentiation of this lung primordium into the bronchial and pulmonary acinar systems begins during this period. The restriction of cell types and in some cases loss of cell-specific markers herald changes in the stage of bronchiolar versus distal epithelial cell fate and differentiation (48,58). These processes of airway branching and cytodifferentiation require a close interaction between endodermal epithelium and adjacent mesenchyme and are affected by specific factors and hormonal systems active in the developing embryo and fetus (1,22,24,35,38). In particular, in rodent lung organ cultures and human lung explant cultures, triiodothyronine (T 3 ), the active form of thyroid hormone, influences late fetal lung development by accelerating epithelial cell differentiation leading to surfactant phospholipid synthesis and by regulating lung structural development and alveolar septation (9,11,26,38). Little is known about the cellular expression pattern of T 3 receptors during fetal lung development, but they are present in rodent and human lung tissue during the pseudoglandular period and increase in quantity and binding affinity as lung development progresses (6,13,18,20,23). Although there are relatively low levels of T 3 and its receptors in early fetal life, maternal hypo-or hyperthyroidism le...

show abstract

Section: Discussionsupporting

confidence: 87%

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Archavachotikul

Ciccone

Chinoy

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the mouse and rat, thyroid hormone affects lung epithelial and mesenchymal differentiation, lung branching morphogenesis, and postnatal alveolar maturation (Archavachotikul et al, 2002;Massaro et al, 1986;Volpe et al, 2003). However, Tpst2−/− mice have normal postnatal viability (Borghei et al, 2006) and their lungs are histological normal at P1 and beyond (data not shown) despite the presence of severe hypothyroidism.…”

Section: Discussionmentioning

confidence: 94%

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Westmuckett

Hoffhines

Borghei

et al. 2008

General and Comparative Endocrinology

View full text Add to dashboard Cite

Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). Tpst double knockouts were generated to investigate the importance of tyrosine sulfation in vivo. Double knockouts were born alive at the expected frequency, were normal in size, and their tissues do not synthesize sulfotyrosine. However, most pups die in the early postnatal period with signs of cardiopulmonary insufficiency. A combination of clinical, magnetic resonance imaging, and histological data indicated that lungs of Tpst double knockouts fail to expand at birth resulting in acute pulmonary hypertension, right-to-left shunting, and death by asphyxia in the early postnatal period. Some double knockouts survive the postnatal period, but fail to thrive and display delayed growth that is due in part to hypothyroidism. In addition, we find that Tpst2−/− mice have primary hypothyroidism, but that Tpst1−/− mice are euthyroid. This suggests that a protein(s) required for thyroid hormone production is sulfated and cannot be sulfated in the absence of TPST-2. Thus, Tpst1 and Tpst2 are the only Tpst genes in mice, tyrosine sulfation is required for normal pulmonary function at birth, and TPST-2 is required for normal thyroid gland function.

show abstract

“…Scale Bar=10 μm (a) Scale Bars= 100 μm (b-f). Tissue sections treated with pooled rabbit IgG gave no detectable staining (f and data not shown) 5-17 in human development (Van Tuyl and Post 2003;Volpe et al 2003). CCN5 was present in GD14 and GD16 bronchial epithelium and in GD16 mesenchymal cells surrounding branching bronchioles (Fig.…”

Section: Respiratory Systemmentioning

confidence: 91%

CCN5 expression in mammals

Jones

Gray

Oliveira

et al. 2007

J. Cell Commun. Signal.

View full text Add to dashboard Cite

The six proteins of the CCN family have important roles in development, angiogenesis, cell motility, proliferation, and other fundamental cell processes. To date, CCN5 distribution in developing rodents and humans has not been mapped comprehensively. CCN5 strongly inhibits adult smooth muscle cell proliferation and motility. Its antiproliferative action predicts that CCN5 would not be present in developing tissues until the proliferation phase of tissue morphogenesis is complete. However, estrogen induces CCN5 expression in epithelial and smooth muscle cells, suggesting that CCN5 might be widely expressed in embryonic tissues exposed to high levels of estrogen.9-16 day murine embryos and fetuses and 3-7 month human fetal tissues were analyzed by immunohistochemistry. CCN5 was detected in nearly all developing tissues. CCN5 protein expression was initially present in most tissues, and at later times in development tissue-specific expression differences were observed. CCN5 expression was particularly strong in vascular tissues, cardiac muscle, bronchioles, myotendinous junctions, and intestinal smooth muscle and epithelium. CCN5 expression was initially absent in bone cartilaginous forms but was increasingly expressed during bone endochondral ossification. Widespread CCN5 mRNA expression was detected in GD14.5 mice. Although CCN2 and CCN5 protein expression patterns in some adult pathologic conditions are inversely expressed, this expression pattern was not found in developing mouse and human tissues. The widespread expression pattern of CCN5 in most embryonic and fetal tissues suggests a diverse range of functions for CCN5.

show abstract

Thyroid hormone affects distal airway formation during the late pseudoglandular period of mouse lung development

Cited by 8 publications

References 44 publications

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

CCN5 expression in mammals

Contact Info

Product

Resources

About