title: Hepatocyte growth factor is constitutively produced by donor-derived bone marrow cells and promotes regeneration of pancreatic beta-cells.
abstract: 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.
authors.affiliation: Department of General and Gastrointestinal Surgery, Showa University, School of Medicine, Tokyo, Japan. yoshi-i@rj8.so-net.ne.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Izumida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aoki
authors.forename: Dausuke
authors.initials: D
authors.lastname: Yasuda
authors.forename: Tomotake
authors.initials: T
authors.lastname: Koizumi
authors.forename: Chisaki
authors.initials: C
authors.lastname: Suganuma
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Murai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Ken
authors.initials: K
authors.lastname: Hayashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Odaira
authors.forename: Tomakazu
authors.initials: T
authors.lastname: Kusano
authors.forename: Miki
authors.initials: M
authors.lastname: Kushima
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kudano
mesh_terms: 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
chemical_list: D007328:Insulin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met