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PMID: 2466294 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Regulation of intestinal epithelial cell growth by transforming growth factor type beta.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 5 ·1989-03-00 ·Pages 1578-82

Barnard JA, Beauchamp RD, Coffey RJ, Moses HL

Abstract

A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type beta 1 (TGF-beta 1) mRNA, secretes latent 125I-labeled TGF-beta 1 competing activity into culture medium, and binds 125I-labeled TGF-beta 1 to specific, high-affinity (Kd = 3.7 pM) cell surface receptors. IEC-6 cell growth is markedly inhibited by TGF-beta 1 and TGF-beta 2 with half-maximal inhibition occurring between 0.1 and 1.0 ng of TGF-beta 1 per ml. TGF-beta 1-mediated growth inhibition is not associated with the appearance of biochemical markers of enterocyte differentiation such as alkaline phosphatase expression and sucrase activity. TGF-beta 1 (10 ng/ml) increases steady-state levels of its own mRNA expression within 8 hr of treatment of rapidly growing IEC-6 cells. In freshly isolated rat jejunal enterocytes that are sequentially eluted from the crypt villus axis, TGF-beta 1 mRNA expression is most abundant in terminally differentiated villus tip cells and least abundant in the less differentiated, mitotically active crypt cells. We conclude that TGF-beta 1 is an autoregulated growth inhibitor in IEC-6 cells that potentially functions in an autocrine manner. In the rat jejunal epithelium, TGF-beta 1 expression is most prominently localized to the villus tip--i.e., the region of the crypt villus unit that is characterized by the terminally differentiated phenotype. These data suggest that TGF-beta 1 may function in coordination of the rapid cell turnover typical for the intestinal epithelium.

MeSH Terms
Animals Cell Differentiation Cell Division/drug effects Cells, Cultured Culture Media DNA Replication Epithelial Cells Jejunum/cytology Kinetics Poly A/isolation & purification RNA/isolation & purification RNA, Messenger Rats Transforming Growth Factors/biosynthesis,genetics,pharmacology
Chemicals
Culture Media RNA, Messenger Poly A RNA Transforming Growth Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Barnard J A
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Beauchamp R D
Coffey R J
Moses H L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.5.1578
Published
1989-03-00
Pages
1578-82
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC286741
Subset
IM
Grants
NCI NIH HHS · CA46413 · United States
NCRR NIH HHS · RR05424 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.5.1578 PMC Full Text View journal details
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