Delayed liver regeneration in mice lacking liver serum response factor.
Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.
Latasa
M Ujue
MU
Institut Cochin, Genetics and Development Department, 24 Rue du Fbg St. Jacques, 75014 Paris, France.
Couton
Dominique
D
Charvet
Claude
C
Lafanechère
Aurélie
A
Guidotti
Jacques-Emmanuel
JE
Li
Zhenlin
Z
Tuil
David
D
Daegelen
Dominique
D
Mitchell
Claudia
C
Gilgenkrantz
Hélène
H
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000502:physiology / Q000601:surgery; D008115:Liver Regeneration / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D026362:Serum Response Factor; D004247:DNA