PMID- 33588415 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1422-6421 (Electronic) IS - 1422-6405 (Linking) VI - 209 IP - 4-6 DP - 2020 TI - Soluble Epoxide Hydrolase as an Important Player in Intestinal Cell Differentiation. PG - 177-188 LID - 10.1159/000512807 [doi] AB - There is growing evidence that soluble epoxide hydrolase (sEH) may play a role in cell differentiation. sEH metabolizes biologically highly active and generally cytoprotective epoxyeicosatrienoic acids (EETs), generated from arachidonic acid metabolism by CYP epoxygenases (CYP2C and CYP2J subfamilies), to less active corresponding diols. We investigated the effect of sEH inhibitor (TPPU) on the expression of villin, CYP2C8, CYP2C9, CYP2J2, and sEH in undifferentiated and in vitro differentiated HT-29 and Caco2 cell lines. The administration of 10 muM TPPU on differentiated HT-29 and Caco2 cells resulted in a significant decrease in expression of villin, a marker for intestinal cell differentiation. It was accompanied by a disruption of the brush border when microvilli appeared sparse and short in atomic force microscope scans of HT-29 cells. Although inhibition of sEH in differentiated HT-29 and Caco2 cells led to an increase in sEH expression in both cell lines, this treatment had an opposite effect on CYP2J2 expression in HT-29 and Caco2 cells. In addition, tissue samples of colorectal carcinoma and adjacent normal tissues from 45 patients were immunostained for sEH and villin. We detected a significant decrease in the expression of both proteins in colorectal carcinoma in comparison to adjacent normal tissue, and the decrease in both sEH and villin expression revealed a moderate positive association. Taken together, our results showed that sEH is an important player in intestinal cell differentiation. CI - (c) 2021 S. Karger AG, Basel. FAU - Cizkova, Katerina AU - Cizkova K AD - Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia. FAU - Koubova, Katerina AU - Koubova K AD - Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia. FAU - Foltynkova, Tereza AU - Foltynkova T AD - Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia. FAU - Jiravova, Jana AU - Jiravova J AD - Department of Medical Biophysics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia. FAU - Tauber, Zdenek AU - Tauber Z AD - Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia, zdenek.tauber@upol.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210215 PL - Switzerland TA - Cells Tissues Organs JT - Cells, tissues, organs JID - 100883360 RN - 0 (Eicosanoids) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2J2) RN - EC 3.3.2.- (Epoxide Hydrolases) SB - IM MH - Caco-2 Cells MH - *Cell Differentiation MH - Colorectal Neoplasms MH - Cytochrome P-450 CYP2J2 MH - Cytochrome P-450 Enzyme System MH - Eicosanoids MH - Epoxide Hydrolases MH - Humans OTO - NOTNLM OT - Arachidonic acid metabolism OT - Brush border OT - Cell differentiation models OT - Colorectal carcinoma OT - Soluble epoxide hydrolase inhibitor EDAT- 2021/02/16 06:00 MHDA- 2021/12/24 06:00 CRDT- 2021/02/15 20:17 PHST- 2020/07/20 00:00 [received] PHST- 2020/11/05 00:00 [accepted] PHST- 2021/02/16 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/02/15 20:17 [entrez] AID - 000512807 [pii] AID - 10.1159/000512807 [doi] PST - ppublish SO - Cells Tissues Organs. 2020;209(4-6):177-188. doi: 10.1159/000512807. Epub 2021 Feb 15.