Loss of RegI in conjunction with gastrin deficiency in mice facilitates efficient gastric ulcer healing but is dispensable for hyperplasia and tumourigenesis.
RegI (Regenerating islet derived-1) was originally characterized as a growth factor involved in pancreatic islet cell regeneration. It is also considered a gastrointestinal mitogen as its expression is increased during pathologies involving aberrant cell proliferation that can lead to neoplasia. However, the absolute requirement for RegI to directly stimulate gastric mucosal cell proliferation in vivo requires further investigation. We used RegI-deficient mice to determine the requirement for RegI in normal gastric mucosal development, wound healing, hyperplasia and tumourigenesis. We found that epithelial repair of acetic acid ulcers in compound mutant RegI/gastrin-deficient mice was significantly reduced compared to wild type, RegI-deficient or gastrin-deficient mice. In contrast, RegI was dispensable for normal gastric mucosal development, hyperplasia in HKbeta-deficient mice and tumourigenesis in gp130(F/F) mice. Although RegI was not required for proliferation in these pathological models, expression of multiple Reg family members were increased during gp130(F/F) tumourigenesis. Interestingly, loss of RegI in gp130(F/F) mice resulted in decreased expression of other Reg family members. Our results indicate that RegI and gastrin may synergistically regulate gastric mucosal proliferation during certain pathological settings like wound healing while gastric epithelial proliferation in other pathologies may require coordinated expression of multiple Reg genes.
Peterson
Anthony J
AJ
GRIP Lab (Gastrointestinal Research, Inflammation & Pathology), Murdoch Children's Research Institute, Parkville 3052, Australia.
Nguyen
Nhung
N
Okamoto
Hiroshi
H
Giraud
Andrew S
AS
van Driel
Ian R
IR
Judd
Louise M
LM
D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000166:cytology; D005755:Gastrins / Q000172:deficiency* / Q000235:genetics; D006965:Hyperplasia / Q000503:physiopathology*; D015151:Immunoblotting; D051847:Lithostathine / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013274:Stomach Neoplasms / Q000503:physiopathology*; D013276:Stomach Ulcer / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics
D005755:Gastrins; D051847:Lithostathine; C497615:Reg1 protein, mouse