Open AccessRole of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells
Author(s) -
Tasuku Konno,
Takenori Kotani,
Jajar Setiawan,
Yuka Nishigaito,
Naoki Sawada,
Shinya Imada,
Yasuyuki Saito,
Yoji Murata,
Takashi Matozaki
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0215255
Subject(s) - lysophosphatidic acid , organoid , intestinal epithelium , microbiology and biotechnology , mapk/erk pathway , cellular differentiation , enteroendocrine cell , epidermal growth factor , intestinal mucosa , kinase , biology , signal transduction , chemistry , epithelium , biochemistry , medicine , receptor , genetics , endocrine system , gene , hormone
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.