The Relationship Between Lymphangiogenesis and Liver Regeneration After Partial Hepatectomy in Cholestatic Mice. 2020

Takashi Hamada, and Masaaki Hidaka, and Mitsuhisa Takatsuki, and Yusuke Sakai, and Haung Yu, and Koji Natsuda, and Shinichiro Ono, and Tomohiko Adachi, and Akihiko Soyama, and Susumu Eguchi
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences/Nagasaki University Hospital, Nagasaki, Japan.

The mechanisms of lymphangiogenesis in the cholestatic liver after partial hepatectomy (PH) remain unclear. We aimed to demonstrate the relationship between lymphangiogenesis and liver regeneration after partial hepatectomy in the cholestatic liver. C57BL/6 mice were subjected to 70% partial hepatectomy only (PH group, n = 20) and 70% partial hepatectomy with temporary common bile duct (BD) obstruction by clipping (BD+PH group, n = 20). Five mice per group were sacrificed at 1, 3, 5, and 7 days after the procedure. The liver function was examined by blood tests, and the liver regeneration rate was assessed by body weight and liver weight. Immunohistochemical staining of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) showed liver lymphangiogenesis. The gene expression of lymphangiogenesis-associated factors (e.g., vascular endothelial growth factor receptor-3 [VEGFR-3]) was examined by a real-time polymerase chain reaction. The liver function in the BD+PH group was worse than that in the PH group on postoperative day 1 (POD1) (aspartate aminotransferase: 6528 ± 1641 U/L vs. 2741 ± 368 U/L, p < 0.05, alanine aminotransferase: 4160 ± 1255 U/L vs. 2315 ± 357 U/L, total bilirubin: 1.36 ± 1.16 mg/dL vs. 0.09 ± 0.01 mg/dL), and the liver regeneration rate in the BD+PH group was worse on POD7 (4.57% vs. 5.91%, p < 0.05). The LYVE-1 expression in Glisson's capsule peaked on POD5 and POD7 in the PH and BD+PH groups, respectively. The peak gene expression of VEGFR-3 in the BD+PH group was delayed in comparison with the PH group. Lymphangiogenesis after partial hepatectomy in the cholestatic liver was suggested to be delayed due to impaired liver regeneration and the late expression of VEGFR-3.

UI MeSH Term Description Entries
D008115 Liver Regeneration Repair or renewal of hepatic tissue. Liver Regenerations,Regeneration, Liver,Regenerations, Liver
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002779 Cholestasis Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS). Bile Duct Obstruction,Biliary Stasis,Bile Duct Obstructions,Biliary Stases,Cholestases,Duct Obstruction, Bile,Duct Obstructions, Bile,Obstruction, Bile Duct,Obstructions, Bile Duct,Stases, Biliary,Stasis, Biliary
D006498 Hepatectomy Excision of all or part of the liver. (Dorland, 28th ed) Hepatectomies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D042583 Lymphangiogenesis The formation of LYMPHATIC VESSELS. Lymphangiogeneses
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D040321 Vascular Endothelial Growth Factor Receptor-3 A vascular endothelial cell growth factor receptor whose expression is restricted primarily to adult lymphatic endothelium. VEGFR-3 preferentially binds the vascular endothelial growth factor C and vascular endothelial growth factor D and may be involved in the control of lymphangiogenesis. VEGFR-3,FLT4 Protein,Flt-4,Flt 4,Vascular Endothelial Growth Factor Receptor 3

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