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. 2007 Nov;2(2):233-43.
doi: 10.1007/s12263-007-0053-2. Epub 2007 Sep 27.

TGFbeta1 expression in colonic mucosa: modulation by dietary lipids

Affiliations

TGFbeta1 expression in colonic mucosa: modulation by dietary lipids

Fiorella Biasi et al. Genes Nutr. 2007 Nov.

Abstract

Transforming growth factor beta1 (TGFbeta1) is fundamental to maintain the intestinal epithelial cell homeostasis through its control action on cell proliferation, differentiation and apoptosis. TGFbeta1 dysregulation has been observed in several chronic human diseases, including ulcerative colitis, Crohn's disease and colon carcinoma. In the first two conditions, a marked oxidative stress is consistently present, while in the third one, levels of reactive oxygen species tend to be significantly lower than in the surrounding normal tissue. Lipid-derived compounds such as the aldehyde 4-hydroxynonenal (HNE) or cholesterol oxidation products (oxysterols) were shown able to induce expression and synthesis of TGFbeta1, an event which can be detrimental or beneficial, essentially depending on its actual intensity. Understanding how specific dietary lipids may influence the complex molecular signaling underlying this cytokine expression, may provide new indications for therapeutic and preventive strategies in inflammatory bowel diseases and colon carcinoma.

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Figures

Fig. 1
Fig. 1
Integration of the TGFβ1 apoptotic signal by the lipid oxidation end-product 4-hydroxynonenal. TGFβ1 induces apoptosis in epithelial cells through up-regulation of redox-sensitive transcription factors, such as AP-1. This signal may be mediated by either a Smad-dependent or a Smad-independent pathway, which in turn involves activation of JNK signaling. A mechanism is suggested whereby arachidonic acid oxidation products, such as HNE, may contribute to enhancing TGFβ1-induced apoptotis. Besides JNK-mediated transduction, HNE acts on Smad proteins, thereby strengthening this pathway. HNE interaction with the Smad pathway can enhance and sustain JNK signaling through a positive loop. This convergence of signals results in an amplification of TGFβ1-induced apoptotis. AA arachidonic acid; HNE 4-hydroxynonenal; ROS reactive oxygen species; SAPK/JNK stress-activated protein kinase/c-Jun N-terminal kinase; ATF-2 activating transcription factor-2; TGF-β1 transforming growth factor-beta1; SBE STAT (Signal Transduction and Activator of Transcription) binding site

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