Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat.
BACKGROUND
Stem cell factor (SCF) and its receptor, c-kit, are known to play important roles in hematopoiesis, melanogenesis, and gametogenesis. The biologic effects of the SCF/c-kit system are believed to involve survival, proliferation, and migration of early stem cell progeny. Although SCF and c-kit receptor are widely expressed during normal embryonic development, their expression in the adult is limited.


METHODS
The expression of SCF and c-kit genes was examined during liver regeneration via the oval cell compartment utilizing partial hepatectomy (PH) combined with the administration of a noncarcinogenic dose of 2-acetylaminofluorene (AAF) for 8 days (AAF/PH model).


RESULTS
Both the ligand and the receptor genes were expressed during the early stages of oval cell proliferation after partial hepatectomy in the AAF/PH model, while neither simple partial hepatectomy nor AAF administration alone induced a noticeable expression of the SCF/c-kit system. The level of SCF mRNA increased within 12 hours after partial hepatectomy and reached a peak around day 4. Thus, the expression of SCF preceded the major expansion of the oval cell compartment. The level of c-kit transcripts gradually increased from the 12-hour time point and stayed elevated until day 11, when a large proportion of the oval cells differentiated into small basophilic hepatocytes. Separation of liver cells at day 3 in the AAF/PH model into parenchymal and nonparenchymal fractions demonstrated that the expression of both SCF and c-kit receptor genes was restricted to the nonparenchymal cells. Furthermore, in situ hybridization revealed that the c-kit transcripts were restricted to oval cells, whereas the SCF transcripts were expressed in both oval cells and Ito cells.


CONCLUSIONS
The transcripts for the c-kit receptor are expressed in the early progeny of the hepatic stem cells. The SCF/c-kit system may, possibly in combination with other growth factor/receptor systems, be involved in the early activation of the hepatic stem cells as well as in the expansion and differentiation of oval cells.
Fujio
K
K
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Evarts
R P
RP
Hu
Z
Z
Marsden
E R
ER
Thorgeirsson
S S
SS
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor; D013234:Stem Cells / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics
D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D000509:alpha-Fetoproteins; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases