Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/67767

TitleEmbryonic essential myosin light chain regulates fetal lung development in rats
Author(s)Santos, Marta
Moura, Rute S.
Gonzaga, Sílvia
Silva, Cristina Isabel Nogueira
Ohlmeier, Steffen
Correia-Pinto, Jorge
KeywordsAbnormalities, Drug-Induced
Animals
Cardiac Myosins
Female
Hernia, Diaphragmatic
Hernias, Diaphragmatic, Congenital
Humans
Infant, Newborn
Lung
Muscle, Smooth
Myosin Light Chains
Phenyl Ethers
Pregnancy
Proteomics
Rats
Rats, Sprague-Dawley
Tissue Culture Techniques
Vitamin A
Lung hypoplasia
congenital diaphragmatic hernia
smooth muscle
Issue dateSep-2007
PublisherAmerican Thoracic Society
JournalAmerican Journal of Respiratory Cell and Molecular Biology
CitationSantos, M., Moura, R. S., Gonzaga, S., Nogueira-Silva, C., et. al. (2007). Embryonic essential myosin light chain regulates fetal lung development in rats. American journal of respiratory cell and molecular biology, 37(3), 330-338
Abstract(s)Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.
TypeArticle
URIhttp://hdl.handle.net/1822/67767
DOI10.1165/rcmb.2006-0349OC
ISSN1044-1549
e-ISSN1535-4989
Publisher versionhttps://www.atsjournals.org/doi/full/10.1165/rcmb.2006-0349OC
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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