Activation pattern of mitogen-activated protein kinases in early phase of different size liver isografts in rats

Abstract

Mitogen-activated protein kinases (MAPK) play a pivotal role in ischemia reperfusion injuries of heart and liver, but the activation pattern of MAPKs in the early phase of different size liver isografts remains unclear. The experiment is designed to investigate the activation pattern and role of MAPKs in isografts of the rat with different size liver transplantation. The animal models of different size graft liver transplantation (whole graft, 50% size, or 30% size, respectively) were established and the sham operation group served as a control. The recipients were sacrificed at 0.5-, 2-, 6-, and 24-hour time points after transplantation to harvest the graft specimens and blood samples. The serum aspartate amino transferase (AST), alanine amino transferase (ALT) and tumor necrosis factor-␣ (TNF-␣) levels, and histological findings were evaluated. The expressions of the total and phosphorylated p46/p54 JNKs, p38 MAPK, and p42/p44 ERKs were detected by Western blot. The serum ALT and AST levels increased significantly at the 0.5-hour time point and maintained high with the peak levels at the 6-hour time point after liver transplantation. The different sizes of liver isografts did not change the expressions of total p46/ p54JNKs, p38MAPK, and p42/p44 ERKs. While the expressions of phosphorylated p46/p54JNKs, p38 MAPK, and p42/p44 ERKs were either negative or mildly up-regulated in the sham operation group, they were significantly activated in the transplanted liver at the 0.5-hour time point, especially in the 30% size liver transplantation group. In conclusion, the activation of three MAPKs in liver isografts correlates with graft size and the JNK and p38 MAPK are responsible for the graft injury while the ERK signal pathway maybe participate in the regulation of cell growth and differentiation after smallfor-size liver transplantation. (Liver Transpl 2005;11: 1527-1532.) L iver transplantation has been widely used as the therapy for patients with end-stage liver disease. However, the shortage of donor organs limits the application of liver transplantation. In the last 15 years, living donor liver transplantation (LDLT) has been widely used to expand the donor pools. However, because of technical obstacles and early graft loss after microcirculatory damage, more risks are occurred in performing small-for-size liver transplantation.Ischemia/reperfusion (I/R) injury is a multifactor process that affects graft function after liver transplantation, which is characterized by activation of Kuppfer cells, acute phase inflammatory response, microcirculatory disturbances, and apoptosis of sinusoidal endothelial cells (SEC) and hepatocytes. 1 Apart from the common I/R injury, the small-for-size grafts suffer mechanical injury related to hemodynamic forces. Previous studies have demonstrated that transient portal hypertension and subsequent microcirculatory disturbances are the major problems occurring in the early phase of small-for-size liver transplantation. [2][3][4][5][6] However, the molecular mechanism of small-for-si...

Hepatic Regenerative Response in Small-Sized Liver Isografts in the Rat

“…Our present study demonstrated that p42/p44 ERKs were significantly up-regulated in small-for-size liver grafts, accompanied by increased cell cycle progression and enhanced proliferative response. This finding further supports the notion that ERK signals may play an important role in I/R and small-for-size graft injury and liver regeneration as well [39,40]. However, the mechanism by which MAPK regulates gene expression and subsequently improves liver regeneration remains unclear and needs further investigation.…”

Growth failure and outcomes in infants with biliary atresia: A report from the Biliary Atresia Research Consortium

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“…The protein was extracted from freshly frozen tissue specimens and subjected to WB analysis as described (Liang et al 2005). BrieXy, the protein concentrations were determined with bovine serum albumin (BSA) as the reference standard using Bio-Rad DC protein assay kit (500-0116, Bio-Rad, Richmond, CA).…”