scholarly journals Transforming Growth Factor-β Stimulates Intestinal Epithelial Focal Adhesion Kinase Synthesis via Smad- and p38-Dependent Mechanisms

2008 ◽  
Vol 173 (2) ◽  
pp. 385-399 ◽  
Author(s):  
Mary F. Walsh ◽  
Dinakar R. Ampasala ◽  
James Hatfield ◽  
Richard Vander Heide ◽  
Silke Suer ◽  
...  
1994 ◽  
Vol 72 (11) ◽  
pp. 1272-1276 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
C. Gurbindo ◽  
E. Levy

The capacity of immature intestinal epithelial crypt cells to synthesize lipids and the factors that promote their differentiation remain largely unknown. We examined the profile of lipids synthesized by a normal rat intestinal epithelial crypt cell line (IEC-6) and determined the effects of transforming growth factor β (TGFβ), a putative crypt cell differentiating factor, on their lipid handling. Incubation of IEC-6 cells with [14C]oleic acid (20 h) resulted in lipid esterification and synthesis, mainly as triglycerides (TGs, 57 ± 0.6%) and phospholipids (PLs, 30 ± 0.6%), with a PL/TG ratio of 0.53. When cells were pulsed (2.5 h) with [14C]oleic acid and then maintained 20 h in medium alone, a significant elevation of the PL/TG ratio (10.2 ± 1.3, p < 0.01) was observed, primarily accounted for by a significant decrease of the TG fraction (p < 0.01). IEC-6 cells secreted only trace amounts of lipids under the latter experimental condition. Incubation with TGFβ (20 h) significantly inhibited IEC-6 cell proliferation but did not promote the expression of cell sucrase activity. TGFβ induced a significant increase in the cellular composition of PL (p < 0.05) and a decrease in the TG fraction (p < 0.02), after a 2.5-h pulse of [14C]oleic acid. Lipid production was unaffected by TGFβ during the 20-h incubation with [14C]oleic acid. Lipid secretion into the medium remained negligible in the presence of TGFβ, after 2.5 h of incubation with substrate as above. Our findings suggest that immature crypt IEC-6 cells are capable of lipid esterification and synthesis but secrete minute amounts of lipoproteins. The predominant lipid fraction synthesized depended upon the availability of fatty acid substrate, with longer incubations favoring TG synthesis and brief cultures generating mainly PLs. The latter tendency was enhanced by TGFβ, which did not induce crypt cell maturation under the conditions tested.Key words: intestinal crypt epithelial cells, transforming growth factor β, triglycerides, phospholipids, enterocyte differentiation.


2008 ◽  
Vol 99 (3) ◽  
pp. 449-454 ◽  
Author(s):  
Wai Ling Chow ◽  
Yuan Kun Lee

Fucose is present in foods, and it is a major component of human mucin glycoproteins and glycolipids.l-Fucose can also be found at the terminal position of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signalling pathways. Mucin fucose can be released through the hydrolytic activity of pathogens and indigenous bacteria, leading to the release of free fucose into the intestinal lumen. The immunomodulating effects of free fucose on intestinal epithelial cells (enterocyte-like Caco-2) were investigated. It was found that the presence ofl-fucose up regulated genes and secretion of their encoded proteins that are involved in both the innate and adaptive immune responses, possibly via the toll-like receptor-2 signalling pathway. These include TNFSF5, TNFSF7, TNF-α, IL12, IL17 and IL18.Besides modulating immune reactions in differentiated Caco-2 cells, fucose induced a set of cytokine genes that are involved in the development and proliferation of immune cells. These include the bone morphogenetic proteins (BMP) BMP2, BMP4, IL5, thrombopoietin and erythropoietin. In addition, the up regulated gene expression of fibroblast growth factor-2 may help to promote epithelial cell restitution in conjunction with the enhanced expression of transforming growth factor-β mRNA. Since the exogenous fucose was not metabolised by the differentiated Caco-2 cells as a carbon source, the reactions elicited were suggested to be a result of the direct interaction of fucose and differentiated Caco-2 cells. The presence of free fucose may signal the invasion of mucin-hydrolysing microbial cells and breakage of the mucosal barrier. The intestinal epithelial cells respond by up regulation and secretion of cytokines, pre-empting the actual invasion of pathogens.


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