Total parenteral nutrition leads to alteration of hepatocyte cell cycle gene expression and proliferation in the mouse.
Total parenteral nutrition (TPN) is correlated with progressive liver injury. Such injury may be associated with either an increase or decrease in hepatocyte growth. The goal of these experiments was to determine TPN-related alterations in intrahepatic genes, as they relate with the cell cycle, using microarray techniques. After 7 days of infusion of saline or TPN-solution, hepatocyte gene expression was examined with a 5000-cDNA microarray chip. TPN was associated with an up-regulation of the cyclin kinase Cdc25B mRNA, which controls the cell cycle at the G2/M phase. Based on this, our studies were directed at alterations in genes related to mitosis in this phase of the cell cycle. mRNA expression of mitotic phase inducers and inhibitors were examined. Cdc25B1 mRNA expression increased with TPN. TPN also led to additional significant alterations in the expression of other factors which mediate proliferation in this phase of mitosis. Histologically, TPN resulted in a significant decline in hepatocyte proliferation. Coincident with the alteration in cyclin expression was a significant decrease in hepatocytes in the G2/M phase with TPN administration. This study demonstrates significant alterations in cell cycle gene expression with TPN. The findings correlate with a loss of hepatocyte proliferation and may give insight into the potential mechanism of TPN-induced hepatocyte injury.
Tazuke
Yuko
Y
Section of Pediatric Surgery, C.S. Mott Children's Hospital, Department of Surgery, University of Michigan Medical School, F3970 Mott Children's Hospital, Box 0245, Ann Arbor, MI 48109, USA.
Wildhaber
Barbara E
BE
Yang
Hua
H
Washburn
Joseph
J
Teitelbaum
Daniel H
DH
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D018816:Genes, cdc; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics*
D018797:Cell Cycle Proteins; D016213:Cyclins; D012333:RNA, Messenger; D020687:cdc25 Phosphatases