Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice. Hepatology 2009 May;49(5):1645-54
Date
02/11/2009Pubmed ID
19205030Pubmed Central ID
PMC2810404DOI
10.1002/hep.22834Scopus ID
2-s2.0-66149117384 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
UNLABELLED: 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.
CONCLUSION: SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression.
Author List
Sun K, Battle MA, Misra RP, Duncan SAAuthor
Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Glucose
Body Size
Cell Proliferation
Cell Survival
Female
Gene Expression
Hepatocytes
Insulin-Like Growth Factor I
Liver
Male
Mice
Mice, Knockout
Organ Size
Organogenesis
Serum Response Factor
Triglycerides
