Linked Life Data

9950213

Source:http://linkedlifedata.com/resource/pubmed/id/9950213

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-4-13
pubmed:abstractText
The two major intestinal epithelial cell lineages are columnar fluid-absorbing cells and mucin-producing goblet cells. High levels of transforming growth factor (TGF) beta1 are found surrounding postmitotic cells in the colonic crypt, suggesting that TGF-beta1 mediates the maturation and growth inhibition of both epithelial cell types. However, we now show that the injection of recombinant TGF-beta1 into mice leads to an enrichment of goblet cells, indicating that these normal epithelial cells are resistant to TGF-beta1. In support of this interpretation, each of two independently isolated cell lines modeling normal colon goblet cells was also growth resistant to exogenous TGF-beta1 but made levels of TGF-beta receptor (TbetaR) I, TbetaRII, and TbetaIII mRNA and protein equal to those made by two TGF-beta1-sensitive cell lines. No mutations were found in the alk5 or alk2 forms of TbetaRI or in TbetaRII; these receptors were found on the cell surface, although they could not bind 125I-labeled TGF-beta1. TbetaRIII binds TGF-beta1, concentrates it, and presents it to TbetaRII. The major TbetaRIII form, betaglycan, did not undergo normal posttranslational modification in either of the goblet cell lines and could not bind 125I-labeled TGF-beta1; thus, it was nonfunctional. TGF-beta resistance was overcome by raising TGF-beta1 levels 100-fold, at which point TbetaRII could bind TGF-beta1. Signaling initiated by these higher TGF-beta1 levels was blocked by the expression of dominant negative TbetaRII, demonstrating that TbetaRII and TbetaRI were functional. Cells resistant to exogenous TGF-beta1 maintained functional cell surface TbetaRI and TbetaRII to mediate responses to autocrine TGF-beta1, which controlled the maturation of the adhesion protein integrin beta1. Expression of dominant negative TbetaRII in goblet cells greatly inhibited the conversion of the beta1 integrin from its precursor to its mature form. Thus, in normal intestinal epithelial goblet cells, TbetaRI and TbetaRII can respond to autocrine but not exogenous TGF-beta without the participation of TbetaRIII. Absorptive epithelial cells are growth inhibited by TGF-beta1 both in vivo and in vitro; therefore, the loss of functional TbetaRIIIs on goblet cells allows differential regulation of the two major intestinal epithelial cell types.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Activin Receptors, Type I, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth..., http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/betaglycan, http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Differential responsiveness to autocrine and exogenous transforming growth factor (TGF) beta1 in cells with nonfunctional TGF-beta receptor type III.
pubmed:affiliation
State University of New York Health Science Center, Syracuse 13210, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't