When Activator and Inhibitor of PPARα Do the Same: Consequence for Differentiation of Human Intestinal Cells
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
IGA_LF_2021_005
Univerzita Palackého v Olomouci
PubMed
34572440
PubMed Central
PMC8472525
DOI
10.3390/biomedicines9091255
PII: biomedicines9091255
Knihovny.cz E-zdroje
- Klíčová slova
- cell differentiation, cell proliferation, colorectal carcinoma, peroxisome-proliferator activated receptor,
- Publikační typ
- časopisecké články MeSH
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.
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