Preventive Effect of Fibroblast Growth Factor and Hepatocyte Growth Factor on Ceramide‐Induced Dysfunction Human Small Intestinal Cells

Aim:  To investigate whether TNF‐ is necessary for hepatocyte proliferation, we study liver regeneration after partial hepatectomy in mice lacking TNF receptor‐1.
Methods:  TNF receptor type‐1 knockout mice and wild‐type mice were subjected to two‐thirds partial hepatectomy (PHx). Liver regeneration was evaluated by assessing liver weights and Ki67 immunohistochemistry. Riken cDNA microarray analysis was performed on liver samples from mice undergoing PHx to compare clearly differentiated mouse PHx models (TNFR‐1 knockout mice‐K group, and wild type mice‐W group).
Results:  The cumulative survival after PHx in K group was lower than in W group. The mortality rate in K group during the first 3 days after PHx was higher (33%) than in W group. The time to regain the liver weight in K group was 14 days and 7 days in W group. The plasma IL‐6 levels in K type at 3 hr was significantly higher than in W group. The Ki67 expression in K group at 4 days was lower than in W group. LPS, Toll like receptor 4 precursor and MAPK 8 interacting protein in K group was higher than in W group. For cell cycle‐regulated genes, cyclin D1, NFB light chain and TNF receptor super family membrane 1a in K group was lower than in W group.
Conclusions:  Lack of TNF‐ signaling through TNF receptor type 1 suppresses liver regeneration after partial hepatectomy in spite of enhancement of LPS–JNK pathway, no TNF‐a and IL‐6 pathway.