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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A competent permeability barrier must be present by the end of gestation to allow for life in a terrestrial environment. Indeed, early preterm infants display serious complications of skin immaturity. Yet, regardless of their degree of prematurity, all infants quickly develop a competent barrier. To learn more about the mechanisms and regulation of barrier ontogeny, we have utilized late-gestation fetal rodents. In 19-21 d fetal rats, we showed that barrier competence is accompanied by both enhanced epidermal development and formation of extracellular lamellar membranes in the stratum corneum. The identical sequence and time-course occurs when fetal rat skin is cultured in a serum-free medium. Glucocorticoids, thyroid hormone (T3), and estrogen accelerate, while androgens delay barrier formation both in utero and in the in vitro system, explaining the poorer outcome of premature males versus females. But neither T3 nor glucocorticoids are absolutely required for barrier development. Lifting fetal skin cultures to an air-medium interface also accelerates barrier formation, explaining the rapid emergence of barrier competence in very premature infants. PPARalpha and FXR activators, which, like T3, heterodimerize with the nuclear receptor, RXR, also accelerate barrier development in vitro. Finally, not only the nuclear receptor family, but also Ca++ could regulate key events late in barrier development.
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PMID:Ontogeny of the epidermal permeability barrier. 973 18

We compared proliferation (growth) and differentiation (development) related proteins in normal and hypoplastic fetal murine lungs. The hypoplastic lungs were created in CD-1 fetal mice by nitrofen exposure (25 mg per pregnant mouse given intragastrically on gestational day 8 [Gd8]), as published earlier. The lungs were harvested at Gd14, 16, 19 and from neonates. Immunoblot analyses were carried out for transcription factors (oncogenic proteins, nuclear receptor, and transmembrane receptor proteins) in severely hypoplastic murine fetal lungs with coexistent diaphragmatic hernia, and results were compared with those derived from normal lungs of equivalent age. These proteins have proposed roles in the regulation of proliferation and differentiation processes of fetal lungs. We have shown that the product of the oncogene c-myc was reduced in hypoplastic lungs at all stages of gestation, whereas c-Fos protein levels were variable. These proteins are known to regulate transcription of various developmental proteins, such as those responsible for proliferation and differentiation. Further, the nuclear transcription factors thyroid transcription factor-1 (TITF-1) and glucocorticoid receptor (GR) were reduced, and thyroid hormone receptor (TR) and retinoic acid receptors (RARs) were inhibited in severely hypoplastic lungs compared to normal lungs of equivalent gestational stage, except in neonatal lungs, where signals for RARs were seen. TITF-1 is known to localize in bronchial epithelial cells in developing lungs. It is restricted to type II pneumocytes with gestational development in the normal lungs and regulates surfactant proteins. Earlier, we have reported that surfactant proteins are reduced in hypoplastic lungs. In the current study, reduced GR and TITF-1 proteins may play a role in reducing surfactant proteins in the hypoplastic lungs. The significant inhibition in TR and RARalpha in the severely hypoplastic lungs reflects on affected epithelial cell maturation and alveolar formation, respectively. Altered RARbeta levels correlate with affected lung growth and branching morphogenesis of nitrofen-exposed lungs. A transmembrane receptor protein EGFR was reduced in hypoplastic lungs, suggesting the involvement of altered mesenchymal-epithelial signal transduction pathways. We conclude (1) Our data suggest altered levels of various nuclear transcription factors in the murine fetal hypoplastic lungs; (2) Reduced levels TITF-1 protein in hypoplastic lungs may have caused the functional immaturity of distal lung, immature airways and thus may affect overall differentiation of lungs. These results correlated with low levels of surfactant proteins in these lungs; (3) TR and RAR inhibition indicate their roles through reduced or retarded proliferation and differentiation processes in the severely hypoplastic lungs; (4) GR down-regulation in developing fetal murine hypoplastic lungs indicate delayed development, and GR up-regulation in affected neonates may be induced by stress/stretch caused at birth due to air-breathing; (5) Down- regulation of EGFR indicate altered mesenchymal-epithelial interactions and possible influence on lung proliferation and differentiation.
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PMID:Down-regulation of regulatory proteins for differentiation and proliferation in murine fetal hypoplastic lungs: altered mesenchymal-epithelial interactions. 1147 30

Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3. These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors.
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PMID:Retinoic acid maintains human skeletal muscle progenitor cells in an immature state. 2802 71