title: FoxA2 involvement in suppression of protein C, an outcome predictor in experimental sepsis.
abstract: 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.
authors.affiliation: Biotechnology Discovery Research, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Berg
authors.forename: Bruce
authors.initials: B
authors.lastname: Gerlitz
authors.forename: Ganesh R
authors.initials: GR
authors.lastname: Sharma
authors.forename: Mark A
authors.initials: MA
authors.lastname: Richardson
authors.forename: Eddie J
authors.initials: EJ
authors.lastname: Stephens
authors.forename: Renee L
authors.initials: RL
authors.lastname: Grubbs
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Holmes
authors.forename: Kelly
authors.initials: K
authors.lastname: Fynboe
authors.forename: Dominick
authors.initials: D
authors.lastname: Montani
authors.forename: Martin S
authors.initials: MS
authors.lastname: Cramer
authors.forename: Steven D
authors.initials: SD
authors.lastname: Engle
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Josef G
authors.initials: JG
authors.lastname: Heuer
authors.forename: Brian W
authors.initials: BW
authors.lastname: Grinnell
mesh_terms: 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
chemical_list: D015415:Biomarkers; C496504:Foxa2 protein, rat; D011486:Protein C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051542:Hepatocyte Nuclear Factor 3-beta