Linked Life Data

9501027

Source:http://linkedlifedata.com/resource/pubmed/id/9501027

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-4-9
pubmed:abstractText
Smad genes are recently identified intracellular effectors for receptor signaling in the BMP/activin/TGF-beta pathway. Since TGF-beta ligands are known to inhibit embryonic lung branching morphogenesis, we tested the hypothesis that Smad genes negatively regulate lung organogenesis. Antisense oligodeoxynucleotides were designed to attenuate Smad3 and Smad2 gene expression in embryonic (E11) mouse lungs over 4 days in culture. Endogenous Smad3 and Smad2 mRNA levels were suppressed by 97 and 91%, respectively, in cultured embryonic lungs when antisense oligodeoxynucleotide (40 microM) to Smad was added, compared to scrambled and sense sequence controls. The corresponding Smad3 and Smad2 protein amounts were also decreased respectively by 86 and 90% in lungs treated with Smad3 and Smad2 antisense oligodeoxynucleotide. Phenotypically, Smad antisense oligodeoxynucleotides resulted in a concentration-dependent increase in lung branching: embryonic lung branching was stimulated by up to 53% in culture with 40 microM antisense oligodeoxynucleotide, whereas both scrambled and sense controls showed no stimulatory effect. Thus, inhibition of endogenous Smad3 and Smad2 gene expression resulted in stimulation of embryonic lung branching similar to that caused by inhibition of TGF-beta type II receptor expression and signaling (J. Zhao et al., 1996, Dev. Biol. 180, 242-257). Abrogation of Smad4 (DPC4), the downstream mediator of Smad3 and Smad2 proteins, with antisense oligodeoxynucleotide, also resulted in increased branching morphogenesis. Furthermore, while TGF-beta alone inhibited lung branching morphogenesis in culture, addition of exogenous TGF-beta 1 could not overcome the stimulatory effect on lung branching of Smad antisense oligodeoxynucleotide treatment. By immunohistochemistry, Smad proteins were localized mainly to the epithelial cells lining the branching distal airways, indicating that Smad genes could regulate lung morphogenesis through mesoderm-endoderm interaction. Our results demonstrate, for the first time, that abrogation of Smad2 and Smad3 or of Smad4 gene expression stimulated early mouse embryonic lung branching morphogenesis in culture, possibly through reversing the negative influence of endogenous TGF-beta signaling upon lung branching morphogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
194
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
182-95
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9501027-Animals, pubmed-meshheading:9501027-Culture Techniques, pubmed-meshheading:9501027-DNA-Binding Proteins, pubmed-meshheading:9501027-Female, pubmed-meshheading:9501027-Gene Expression Regulation, Developmental, pubmed-meshheading:9501027-Lung, pubmed-meshheading:9501027-Mice, pubmed-meshheading:9501027-Morphogenesis, pubmed-meshheading:9501027-Oligonucleotides, Antisense, pubmed-meshheading:9501027-Polymerase Chain Reaction, pubmed-meshheading:9501027-Pregnancy, pubmed-meshheading:9501027-RNA, Messenger, pubmed-meshheading:9501027-Signal Transduction, pubmed-meshheading:9501027-Smad2 Protein, pubmed-meshheading:9501027-Smad3 Protein, pubmed-meshheading:9501027-Smad4 Protein, pubmed-meshheading:9501027-Trans-Activators, pubmed-meshheading:9501027-Transforming Growth Factor beta
pubmed:year
1998
pubmed:articleTitle
Abrogation of Smad3 and Smad2 or of Smad4 gene expression positively regulates murine embryonic lung branching morphogenesis in culture.
pubmed:affiliation
Department of Surgery, Children's Hospital Los Angeles Research Institute, University of Southern California Schools of Dentistry and Medicine, Los Angeles 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.