FoxA2 involvement in suppression of protein C, an outcome predictor in experimental sepsis.
Low levels of protein C (PC) predict outcome as early as 10 h after insult in a rat polymicrobial sepsis model and were associated with suppression of PC mRNA, upstream transcription factor FoxA2, and cofactor hepatocyte nuclear factor 6 (HNF6). Small interfering RNA suppression of FoxA2 in isolated hepatocytes demonstrated regulation of both its cofactor HNF6 and PC. Our data suggest that reduced FoxA2 may be important in the suppression of PC and resulting poor outcome in sepsis.
Berg
David T
DT
Biotechnology Discovery Research, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Gerlitz
Bruce
B
Sharma
Ganesh R
GR
Richardson
Mark A
MA
Stephens
Eddie J
EJ
Grubbs
Renee L
RL
Holmes
Kimberly C
KC
Fynboe
Kelly
K
Montani
Dominick
D
Cramer
Martin S
MS
Engle
Steven D
SD
Jakubowski
Joseph A
JA
Heuer
Josef G
JG
Grinnell
Brian W
BW
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D002432:Cecum; D004195:Disease Models, Animal; D005260:Female; D051542:Hepatocyte Nuclear Factor 3-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008026:Ligation; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D011379:Prognosis; D011486:Protein C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011677:Punctures; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality
D015415:Biomarkers; C496504:Foxa2 protein, rat; D011486:Protein C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051542:Hepatocyte Nuclear Factor 3-beta