Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells.
Intestinal epithelial cells (IECs) are regenerated continuously from intestinal stem cells (ISCs) near the base of intestinal crypts in order to maintain homeostasis and structural integrity of intestinal epithelium. Epidermal growth factor (EGF) is thought to be important to drive the proliferation...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0215255 |
| _version_ | 1819147139617390592 |
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| author | Tasuku Konno Takenori Kotani Jajar Setiawan Yuka Nishigaito Naoki Sawada Shinya Imada Yasuyuki Saito Yoji Murata Takashi Matozaki |
| author_facet | Tasuku Konno Takenori Kotani Jajar Setiawan Yuka Nishigaito Naoki Sawada Shinya Imada Yasuyuki Saito Yoji Murata Takashi Matozaki |
| author_sort | Tasuku Konno |
| collection | DOAJ |
| description | Intestinal epithelial cells (IECs) are regenerated continuously from intestinal stem cells (ISCs) near the base of intestinal crypts in order to maintain homeostasis and structural integrity of intestinal epithelium. Epidermal growth factor (EGF) is thought to be important to drive the proliferation and differentiation of IECs from ISCs, it remains unknown whether other growth factors or lipid mediators are also important for such regulation, however. Here we show that lysophosphatidic acid (LPA), instead of EGF, robustly promoted the development of intestinal organoids prepared from the mouse small intestine. Indeed, LPA exhibited the proliferative activity of IECs as well as induction of differentiation of IECs into goblet cells, Paneth cells, and enteroendocrine cells in intestinal organoids. Inhibitors for LPA receptor 1 markedly suppressed the LPA-promoted development of intestinal organoids. LPA also promoted the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in intestinal organoids, whereas inhibition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 significantly suppressed the development of, as well as the proliferative activity and differentiation of, intestinal organoids in response to LPA. Our results thus suggest that LPA is a key factor that drives the proliferation and differentiation of IECs. |
| first_indexed | 2024-12-22T13:25:04Z |
| format | Article |
| id | doaj.art-79f9ee7918c6429f9585682d2e650dc1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T13:25:04Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-79f9ee7918c6429f9585682d2e650dc12022-12-21T18:24:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021525510.1371/journal.pone.0215255Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells.Tasuku KonnoTakenori KotaniJajar SetiawanYuka NishigaitoNaoki SawadaShinya ImadaYasuyuki SaitoYoji MurataTakashi MatozakiIntestinal epithelial cells (IECs) are regenerated continuously from intestinal stem cells (ISCs) near the base of intestinal crypts in order to maintain homeostasis and structural integrity of intestinal epithelium. Epidermal growth factor (EGF) is thought to be important to drive the proliferation and differentiation of IECs from ISCs, it remains unknown whether other growth factors or lipid mediators are also important for such regulation, however. Here we show that lysophosphatidic acid (LPA), instead of EGF, robustly promoted the development of intestinal organoids prepared from the mouse small intestine. Indeed, LPA exhibited the proliferative activity of IECs as well as induction of differentiation of IECs into goblet cells, Paneth cells, and enteroendocrine cells in intestinal organoids. Inhibitors for LPA receptor 1 markedly suppressed the LPA-promoted development of intestinal organoids. LPA also promoted the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in intestinal organoids, whereas inhibition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 significantly suppressed the development of, as well as the proliferative activity and differentiation of, intestinal organoids in response to LPA. Our results thus suggest that LPA is a key factor that drives the proliferation and differentiation of IECs.https://doi.org/10.1371/journal.pone.0215255 |
| spellingShingle | Tasuku Konno Takenori Kotani Jajar Setiawan Yuka Nishigaito Naoki Sawada Shinya Imada Yasuyuki Saito Yoji Murata Takashi Matozaki Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. PLoS ONE |
| title | Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. |
| title_full | Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. |
| title_fullStr | Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. |
| title_full_unstemmed | Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. |
| title_short | Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells. |
| title_sort | role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells |
| url | https://doi.org/10.1371/journal.pone.0215255 |
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