Fibroblasts and transforming growth factor beta induce organization and differentiation of T84 human epithelial cells

Halttunen, Tuula; Marttinen, A.; Rantala, Immo; Kainulainen, Heikki; Mäki, Markku

doi:10.1053/gast.1996.v111.pm8898639

Cited by 100 publications

(93 citation statements)

References 4 publications

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“…The biological functions of HGF in the small and large intestines are not clear, but it is likely that HGF exerts growth-stimulatory effects on intestinal epithelial cells. When colon cancer T84 cells are grown in type I collagen gel, HGF does not induce their differentiation but stimulates their growth (61). Our results showed that PGE 2 -activated myofibroblasts increased the production of HGF, which predominantly stimulated the migration of intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 62%

Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis

et al. 2006

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Prostaglandins (PG) are produced throughout the gastrointestinal tract and are critical mediators for a complex array of physiologic and pathophysiologic processes in the intestine. Intestinal myofibroblasts, which express cyclooxygenase (COX) and generate PGE 2 , play important roles in intestinal epithelial proliferation, differentiation, inflammation, and neoplasia through secreting growth factors and cytokines. Here, we show that PGE 2 activated human intestinal subepithelial myofibroblasts (18Co) through Gs protein-coupled E-prostanoid receptors and the cyclic AMP/protein kinase A pathway. 18Co cells and primary colonic myofibroblast isolates expressed a number of growth factors; several of them were dramatically regulated by PGE 2 . An epidermal growth factor-like growth factor, amphiregulin (AR), which was not expressed by untreated cells, was strongly induced by PGE 2 . Expression of vascular endothelial growth factor A (VEGFA) was rapidly increased by PGE 2 exposure. Hepatocyte growth factor (HGF) was elevated in PGE 2 -treated myofibroblasts at both mRNA and protein levels. Thus, PGE 2 -activated myofibroblasts promoted the proliferation and migration of intestinal epithelial cells, which were attenuated by neutralizing antibodies to AR and HGF, respectively. Moreover, in the presence of PGE 2 , myofibroblasts strongly stimulated the migration and tubular formation of vascular endothelial cells. Neutralizing antibody to VEGFA inhibited the observed stimulation of migration. These results suggest that myofibroblast-generated growth factors are important mediators for PGE 2 -induced intestinal epithelial proliferation and angiogenesis, which play critical roles in intestinal homeostasis, inflammation, and neoplasia. (Cancer Res 2006; 66(2): 846-55)

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Section: Discussionmentioning

confidence: 62%

Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis

et al. 2006

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“…Subsequently, in the adult TGF-␤ is involved in maintaining gut homeostasis through its role in cellular proliferation, differentiation, migration, tissue repair, and apoptosis. Although several studies have suggested the involvement of TGF-␤ in gut epithelial differentiation, such studies are limited and the underlying mechanisms have not been addressed (34,35,69,74). Our work demonstrates that TGF-␤ signaling regulates the expression of intestinal differentiation markers such as IFABP and IAP.…”

Section: Discussionmentioning

confidence: 68%

“…Hexamethylene-bis-acetamide induced HT29 cell differentiation is inhibited by TGF-␤1 neutralizing antibodies (34). Addition of TGF-␤1 is sufficient for induction of differentiation of T84 intestinal epithelial cells cultured in three-dimensional collagen gels and further organization of these differentiated cells into luminal structures resembling crypts, providing definitive evidence for the role of TGF-␤ in intestinal differentiation (35).…”

mentioning

confidence: 85%

Cooperation between GATA4 and TGF-β signaling regulates intestinal epithelial gene expression

Belaguli

Zhang²,

Rigi³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Members of the transforming growth factor-␤ (TGF-␤) family have been shown to play an important role in the regulation of gut epithelial gene expression. We have used the intestinal alkaline phosphatase (IAP) and intestinal fatty acid binding protein (IFABP) promoters to dissect the mechanisms by which TGF-␤1 signaling regulates gut epithelial gene expression. TGF-␤ signaling alone was not sufficient for activation of IAP and IFABP promoters. However, TGF-␤ signaling cooperated with the gut epithelial transcription factor GATA4 to synergistically activate IAP and IFABP promoters. Coexpression of GATA4 along with the TGF-␤1 signal transducing downstream effectors such as Smad2, 3, and 4 resulted in synergistic activation of both IAP and IFABP promoters. This synergistic activation was reduced by simultaneous expression of dominant-negative Smad4. Ϫ40 and Ϫ89 GATA binding sites in the IFABP promoter were required for the synergistic activation by Smad2, 3, and 4 and GATA4. GATA4 and Smad2, 3, and 4 physically associated with each other and this interaction was mediated through the MH2 domain of Smad2, 3, and 4 and the second zinc finger and the COOH-terminal basic domain of GATA4. The COOH-terminal activation domain and the Smad-interacting second zinc finger domain of GATA4 were required for the synergistic activation of the IFABP promoter. Naturally occurring oncogenic mutations within the GATA4-interacting MH2 domain of Smad2 reduced the coactivation of IFABP promoter by Smad2 and GATA4. Our results suggest that the TGF-␤ signaling regulates gut epithelial gene expression by targeting GATA4.

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“…Growth factors, such as IGF-I, EGF, TGF-α and HGF, were expressed in epithelial and stromal cells in mouse uterus and vagina (Shiraga et al, 1997;Brown and Lamartiniere, 2000;Murakami et al, 2001). Several secreted signaling molecules such as TGF-β superfamily members and Wnts have been shown to be implicated in epithelial/stromal interaction at developmental stage (Halttunen et al, 1996;Hammerschmidt et al, 1997;Moon et al, 1997;Robert et al, 1998). But in the adult oviduct, few information is available on diffusible (or growth) factors involved in epithelial/stromal interaction.…”

Section: Discussionmentioning

confidence: 99%

The Mesenchymal Factors Regulating Epithelial Morphogenesis and Differentiation of the Chicken Stomach

Yasugi

Fukuda

2000

Zoological Science

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Fibroblasts and transforming growth factor beta induce organization and differentiation of T84 human epithelial cells

Cited by 100 publications

References 4 publications

Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis

Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis

Cooperation between GATA4 and TGF-β signaling regulates intestinal epithelial gene expression

The Mesenchymal Factors Regulating Epithelial Morphogenesis and Differentiation of the Chicken Stomach

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