Stem cell factor and c-kit are involved in hepatic recovery after acetaminophen-induced liver injury in mice

作者：Hu Bin; Colletti Lisa M^*

来源：American Journal of Physiology - Gastrointestinal and Liver Physiology, 2008, 295(1): G45-G53.

DOI：10.1152/ajpgi.00024.2008

• liver regeneration
• apoptosis
• hepatocyte proliferation
• cytokines

Stem cell factor ( SCF) and its receptor c-kit are important in hematopoiesis and cellular proliferation. c-kit has also been identified as a cell surface marker for progenitor cells. We have previously shown that there is a large reservoir of hepatic SCF, and this molecule plays a significant role in liver regeneration after 70% hepatectomy. In the current study, we further examined the expression of SCF and c-kit in acetaminophen ( APAP)-induced liver injury in C57BL/6J mice or SCF-deficient s1-sld mice and their appropriate wild-type controls. Following APAP-induced liver injury, c-kit mRNA expression increased, with peak levels detected 48 h postinjury. Hepatic SCF mRNA levels after APAP injury were also increased, with peak levels seen 16 h post-APAP. The mortality rate in SCF-deficient mice treated with APAP was significantly higher than that of wild-type mice; furthermore, administration of exogenous SCF significantly reduced the mortality of APAP-treated wild-type mice. Bromodeoxyuridine incorporation experiments showed that SCF significantly increased hepatocyte proliferation at 48 and 72 h in APAP-treated mice. SCF inhibited APAP-induced hepatocyte apoptosis and increased Bcl-2 and Bc1-xL expression, suggesting that this decrease in hepatocyte apoptosis is mediated through Bc1-2 and Bc1-xL. In summary, SCF and c-kit expression was increased after APAP-induced liver injury. Administration of exogenous SCF reduces mortality in APAP-treated mice, increases hepatocyte proliferation, and prevents hepatocyte apoptosis induced by APAP, suggesting that these molecules are important in the liver's recovery from these injuries.

• 出版日期2008-7-1