Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice.
Serum response factor (SRF) is a transcription factor that binds to a CarG box motif within the serum response element of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice had lower blood glucose and triglyceride levels compared with control mice. In addition, Srf(loxP/loxP)AlfpCre mice were smaller and had severely depressed levels of serum insulin-like growth factor 1 (IGF-1). Srf-deficient livers were also smaller than control livers, and liver cell proliferation and viability were compromised. Gene array analysis of SRF depleted livers revealed a reduction in many messenger RNAs, including those encoding components of the growth hormone/IGF-1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes.


CONCLUSIONS
SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression.
Sun
Kai
K
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Battle
Michele A
MA
Misra
Ravi P
RP
Duncan
Stephen A
SA
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D049628:Body Size; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D038081:Organogenesis; D026362:Serum Response Factor / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D026362:Serum Response Factor; D014280:Triglycerides; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I