Aim: Liver regeneration is associated with apoptosis of hepatocytes, which is mediated via tumor necrosis factor receptor 1(TNFR1). The shedding of TNFR1 in liver regeneration and its mechanism to regulate this shedding were investigated.
Methods: The shedding of TNFR1 in liver regeneration and changes of TNF-alpha, PMA and plasma membrane purified from hepatocytes on this shedding process were measured with Western blot. Then, the relationship between TNFR1 shedding and apoptosis of hepatocytes induced by TNFalpha was studied by detecting apoptotic index.
Results: The shedding of TNFR1 began at 4 hours and terminated before 2 months after partial hepatectomy. In culture system, serum from rats at 36 h after partial hepatectomy could also promote this shedding process. With the stimulation of TNFalpha, PMA or purified plasma membrane from hepatocytes at 36 h after partial hepatectomy or from hepatocytes treated with TNFalpha for 2 h, membranous TNFR1 was also shed. With the stimulation of both TNFalpha and plasma membrane from hepatocytes affected with TNFalpha for 2 h or from hepatocytes at 36 h after partial hepatectomy, apoptotic index of hepatocytes decreased from 21 % to 7.52 % and 8.45 %, respectively. PMA could also reduce apoptotic index to 13.67 %. This descent occurred in hepatocytes cultured in serum from rats at 36 h after partial hepatectomy too, but not in serum from rats at 2 months after partial hepatectomy and sham-operated rats.
Conclusion: Shedding of TNFR1 may help reduce apoptosis of hepatocytes induced by TNFalpha. Membrane-anchored metalloprotases could play a role in shedding membranous TNFR1. At the same time, PKC may take part in regulation of this shedding process.