When Activator and Inhibitor of PPARα Do the Same: Consequence for Differentiation of Human Intestinal Cells.

Katerina Cizkova,Zbynek Kamencak,Jiri Hanyk,Zdenek Tauber,Tereza Foltynkova

doi:10.3390/biomedicines9091255

Katerina Cizkova, Zbynek Kamencak + Show 3 more

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https://doi.org/10.3390/biomedicines9091255

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Journal: Biomedicines	Publication Date: Sep 17, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Palacký University, Olomouc

Abstract

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-dependent transcription factor that plays a role in various processes including differentiation of several cell types. We investigated the role of PPARα in the differentiation of intestinal cells using HT-29 and Caco2 cell lines as a model as well as human normal colon and colorectal carcinoma tissues. We detected a significant increase in PPARα expression in differentiated HT-29 cells as well as in normal surface colon epithelium where differentiated cells are localised. Thus, it seems that PPARα may play a role in differentiation of intestinal cells. Interestingly, we found that both PPARα activators (fenofibrate and WY-14643) as well as its inhibitor (GW6471) regulated proliferation and differentiation of HT-29 cells in vitro in the same way. Both compounds led to a decrease in proliferation accompanied by a significant increase in expression of villin, intestinal alkaline phosphatase (differentiation markers). Moreover, the same trend in villin expression was observed in Caco2 cells. Furthermore, villin expression was independent of subcellular localisation of PPARα. In addition, we found similar levels of PPARα expression in colorectal carcinomas in comparison to adjacent normal epithelium. All these findings support the hypothesis that differentiation of intestinal epithelium is PPARα-independent.

Highlights

We examined the effect of Peroxisome proliferator-activated receptor α (PPARα) activators fenofibrate and WY-14643 and PPARα inhibitor GW6471 on cell proliferation activity and expression of villin and intestinal alkaline phosphatase as well as PPARα expression itself
In differentiated HT-29 cells, we found a 2.36-fold higher expression of PPARα in comparison to undifferentiated ones
The villin expression was independent of subcellular localisation of PPARα

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Peroxisome proliferator-activated receptor α (PPARα) is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily. PPARα is activated by a wide range of both endogenous and exogenous ligands such as dietary fatty acids, eicosanoids, hypolipidaemic drugs, phthalates and pesticides [1,2]. PPARs heterodimerise with retinoid X receptor, bind to peroxisome proliferator response elements (PPREs) and regulate the expression of a number of target genes [3]. PPARα regulates various cellular function including energy metabolism, oxidative stress, immune response, xenobiotic metabolism, cell proliferation, differentiation and carcinogenesis [1,2,3,4,5]

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