Three lysophosphatidic acids with a distinct long chain moiety differently affect cell differentiation of human colon epithelial cells to goblet cells

Aim: The intestinal mucus layer helps maintain intestinal homeostasis. In this study, we investigated the effects of lysophosphatidic acids (LPA) on differentiation of human colon carcinoma cell line, HT-29, to goblet cells with and without sodium butyrate, a known differentiation factor for intestinal cells.

Main methods: Number and average size of cells with goblet-like morphology in five photographs per dish were measured for assessment of differentiation of HT-29 cells to goblet cells as well as their relative portion of surface of to whole surface area of the photograph.

Key findings: Our results revealed that 18:1 LPA enhanced butyrate-induced differentiation of HT-29 cells. Because increased mRNA expression of LPA₅ and decreased mRNA expression of LPA₆ were observed in HT-29 cells after treatment with butyrate, we explored the effects of alkyl LPA and 20:4 LPA, which show preferentially higher affinities to LPA₅ and LPA₆, respectively. As a result, the cell differentiation to goblet cell was increased by alkyl LPA but decreased by 20:4 LPA. Further, alkyl LPA and 18:1 LPA, but not 20:4 LPA, were found to reduce the numbers of cells surviving after incubation in a standard culture medium containing 10% fetal calf serum.

Significance: We suggest that the three LPAs positively and negatively affect the differentiation of HT-29 cells to goblet cells, which may be associated with their reduced survival through the activation of distinct LPA receptor(s).