Regulation of intestinal epithelial cell growth by transforming growth factor type beta.
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.
Barnard
J A
JA
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Beauchamp
R D
RD
Coffey
R J
RJ
Moses
H L
HL
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004261:DNA Replication; D004847:Epithelial Cells; D007583:Jejunum / Q000166:cytology*; D007700:Kinetics; D011061:Poly A / Q000302:isolation & purification; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger; D051381:Rats; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology
D003470:Culture Media; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D015291:Transforming Growth Factors