Impaired proliferation of non-parenchymal cells participates in an impairment of liver regeneration in db/db mice.
In this study, we examined the possibility that impaired proliferation of non-parenchymal cells affects in an impairment of liver regeneration in db/db mice, which are congenitally deficient in receptors for leptin. Liver regeneration after a two thirds partial hepatectomy (2/3 PH) was impaired in 10-week-old female db/db mice. The proliferation of both hepatocytes and non-parenchymal cells estimated from a bromodeoxyuridine (BrdU) labeling index was suppressed, and the protein expression of vascular endothelial growth factor was blocked in db/db mice. Although the extent of fatty change and the level of epidermal growth factor receptor protein expression in the liver were improved in 5-week-old db/db mice, the regeneration of liver was impaired after 2/3 PH in both 5- and 10-week-old db/db mice. These results suggested that suppressed proliferation of non-parenchymal cells contributes to the impairment of liver regeneration in db/db mice. As leptin has also the angiogenic effect, the angiogenic inhibitor FR-118487 was administered to ICR mice to examine liver regeneration after 2/3 PH, and the rate of regeneration was affected. In conclusion, it is suggested that the suppressed proliferation of non-parenchymal cells contributes to the impairment of liver regeneration probably through a disrupted angiogenesis in db/db mice.
Uetsuka
Koji
K
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-8657 Tokyo, Japan. akasata@mail.ecc.u-tokyo.ac.jp
Shirai
Makoto
M
Yamauchi
Hirofumi
H
Nakayama
Hiroyuki
H
Doi
Kunio
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000172:deficiency*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013141:Spiro Compounds / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; C096036:FR 118487; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D013141:Spiro Compounds; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors