Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration.
Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca2+]i). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca2+]i, activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system.
Osawa
Hiroyuki
H
Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498, Japan.
Ohnishi
Hirohide
H
Takano
Koji
K
Noguti
Takasi
T
Mashima
Hirosato
H
Hoshino
Hiroko
H
Kita
Hiroto
H
Sato
Kiichi
K
Matsui
Hirofumi
H
Sugano
Kentaro
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053823:Hedgehog Proteins; D007424:Intracellular Fluid / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015534:Trans-Activators / Q000008:administration & dosage*
D053823:Hedgehog Proteins; D015534:Trans-Activators; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium