Hepatocyte growth factor is constitutively produced by donor-derived bone marrow cells and promotes regeneration of pancreatic beta-cells.
Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic b-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of b-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value.The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats.
Izumida
Yoshihiko
Y
Department of General and Gastrointestinal Surgery, Showa University, School of Medicine, Tokyo, Japan. yoshi-i@rj8.so-net.ne.jp
Aoki
Takeshi
T
Yasuda
Dausuke
D
Koizumi
Tomotake
T
Suganuma
Chisaki
C
Saito
Koji
K
Murai
Noriyuki
N
Shimizu
Yoshinori
Y
Hayashi
Ken
K
Odaira
Masanori
M
Kusano
Tomakazu
T
Kushima
Miki
M
Kudano
Mitsuo
M
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism / Q000628:therapy; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D012038:Regeneration; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism
D007328:Insulin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met