The role of hedgehog signaling during gastric regeneration.
BACKGROUND
Hedgehog signaling plays critical roles during embryonic development. It is also involved in tissue regeneration and carcinogenesis in various adult tissues. Moreover, it regulates the maintenance of cancer stem cells and adult stem cells. Although hedgehog signaling is important in gastric carcinogenesis, its role in gastric regeneration has not been previously examined. In the present study, we evaluated the expression and roles of hedgehog signaling during gastric regeneration.


METHODS
Gastric ulcers were induced by serosal application of an acetic acid solution in mice. Sham-operated mice served as controls. The proliferation of gastric progenitor cells was studied using bromodeoxyuridine (BrdU). The expression of hedgehog signaling molecules and the differentiation of gastric progenitor cells were examined by immunohistochemical staining and Western blotting.


RESULTS
One day after the induction of gastric ulcer, the proliferation of gastric progenitor cells increased; however, the expression of hedgehog signaling molecules, including sonic hedgehog (Shh), Indian hedgehog (Ihh), desert hedgehog (Dhh), and patched (Ptch1) decreased at the ulcer margin. From 5 days after the induction of gastric ulcer, newly generated gastric glands and their differentiation were observed at the ulcer margin. The expression of hedgehog signaling molecules gradually increased in the newly generated gastric glands of the ulcer margin. Cyclopamine, a specific inhibitor of hedgehog signaling, significantly inhibited the differentiation of mucous cells and parietal cells during the gastric regeneration process.


CONCLUSIONS
The above results suggest that hedgehog signaling is involved in the differentiation of gastric progenitor cells during the gastric ulcer repair process.
Kang
Dae-Hwan
DH
Department of Internal Medicine, School of Medicine, Pusan National University, Beomeo-Ri, Yangsan, South Korea.
Han
Myoung-Eun
ME
Song
Moo-Ho
MH
Lee
Young-Suk
YS
Kim
Eun-Hee
EH
Kim
Hyun-Jung
HJ
Kim
Gwang-Ha
GH
Kim
Dong-Heon
DH
Yoon
Sik
S
Baek
Sun-Yong
SY
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Oh
Sae-Ock
SO
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D013276:Stomach Ulcer / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014704:Veratrum Alkaloids / Q000494:pharmacology
D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; C000541:cyclopamine