Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 8
pubmed:dateCreated
2009-4-2
pubmed:abstractText
Heparan sulfate proteoglycans (HSPGs) are required for various signaling pathways, one of which is the bone morphogenetic protein (BMP) signaling pathway. N-deacetylase/N-sulfotransferase-1 (NDST1) participates in synthesizing heparan sulfate (HS) chains of HSPGs, and is involved in bone and lung development. Here, we report that in spite of the redundant expression of Ndst2, Ndst3 and Ndst4 genes, Ndst1(-/-) mice display defective differentiation of lung cells and increased cell proliferation. Loss of Ndst1 in the lung enhances downstream BMP signaling in vivo. Noggin, which is an antagonist of BMP, can rescue the Ndst1(-/-) lung morphogenetic defects in explant cultures. Further studies in vitro indicated that loss of Ndst1 significantly impairs BMP internalization by decreasing BMP binding to endogenous HS. Exogenous heparin can rescue both the BMP signaling and BMP internalization abnormalities in Ndst1(-/-) lung. Thus, we propose that HS regulates BMP signaling by controlling the balance between BMP binding to HS, and that BMP receptors and NDST1-dependent modification are essential for this process. The results suggest that NDST1-dependent HS is essential for proper functioning of BMP in embryonic lung development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Heparin, http://linkedlifedata.com/resource/pubmed/chemical/Heparitin Sulfate, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sulfotransferases, http://linkedlifedata.com/resource/pubmed/chemical/heparitin sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/noggin protein
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
122
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1145-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19299468-Animals, pubmed-meshheading:19299468-Bone Morphogenetic Protein 2, pubmed-meshheading:19299468-Bone Morphogenetic Protein 4, pubmed-meshheading:19299468-Bone Morphogenetic Protein Receptors, pubmed-meshheading:19299468-Carrier Proteins, pubmed-meshheading:19299468-Cell Differentiation, pubmed-meshheading:19299468-Cell Proliferation, pubmed-meshheading:19299468-Cells, Cultured, pubmed-meshheading:19299468-Endocytosis, pubmed-meshheading:19299468-Epithelial Cells, pubmed-meshheading:19299468-Gene Expression Regulation, Developmental, pubmed-meshheading:19299468-Gene Expression Regulation, Enzymologic, pubmed-meshheading:19299468-Gestational Age, pubmed-meshheading:19299468-Heparin, pubmed-meshheading:19299468-Heparitin Sulfate, pubmed-meshheading:19299468-Lung, pubmed-meshheading:19299468-Mesoderm, pubmed-meshheading:19299468-Mice, pubmed-meshheading:19299468-Mice, Knockout, pubmed-meshheading:19299468-Organ Culture Techniques, pubmed-meshheading:19299468-Organogenesis, pubmed-meshheading:19299468-RNA, Messenger, pubmed-meshheading:19299468-Signal Transduction, pubmed-meshheading:19299468-Sulfotransferases
pubmed:year
2009
pubmed:articleTitle
NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development.
pubmed:affiliation
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't