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Rapid modulation of liver-specific transcription factors after injury.
Surgery. 1994 Aug; 116(2):285-92; discussion 292-3.S

Abstract

BACKGROUND

The reaction to injury is a well-orchestrated physiologic response involving the coordinated actions of multiple integrated systems. It initially occurs at the molecular level and involves changes in gene transcription. We hypothesized that the molecular mechanisms regulating the generation of an inflammatory response are similar to those orchestrating developmental and tissue-specific expression of proteins and, in the case of the acute phase response, occur through manipulation of liver-specific transcription factors and their binding activity.

METHODS

Female BALB/c mice, 7 to 8 weeks old, were subjected to a 15% body surface area burn. Total and polyadenylated liver RNA was isolated, and Northern blot analysis was performed to determine the kinetics of the acute phase proteins albumin and fibrinogen and the liver-specific transcriptional factors CCAAT-enhancer binding protein (C/EBP) alpha, hepatocyte nuclear factor (HNF)-1 alpha, and HNF-4.

RESULTS

Induction of the injury response was shown by an increase in fibrinogen messenger RNA levels and a decrease in albumin mRNA levels. The liver-specific transcription factor C/EBP alpha decreased after injury and remained significantly lower than control at 3 hours. HNF-4 mRNA levels fell more slowly, reaching significantly lower levels at 6 hours and remaining suppressed at 34 hours. HNF-1 alpha showed the most rapid fall in mRNA levels at 30 minutes after injury and remained significantly below control levels at 34 hours.

CONCLUSIONS

The minimal burn injury model leads to the molecular induction of the acute phase response and induces significant and rapid changes in the liver-specific transcription factors C/EBP alpha, HNF-1 alpha, and HNF-4. These changes may represent a mechanism through which the organ-specific response to injury is mediated.

Authors+Show Affiliations

Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8047996

Citation

Burke, P A., et al. "Rapid Modulation of Liver-specific Transcription Factors After Injury." Surgery, vol. 116, no. 2, 1994, pp. 285-92; discussion 292-3.
Burke PA, Drotar M, Luo M, et al. Rapid modulation of liver-specific transcription factors after injury. Surgery. 1994;116(2):285-92; discussion 292-3.
Burke, P. A., Drotar, M., Luo, M., Yaffe, M., & Forse, R. A. (1994). Rapid modulation of liver-specific transcription factors after injury. Surgery, 116(2), 285-92; discussion 292-3.
Burke PA, et al. Rapid Modulation of Liver-specific Transcription Factors After Injury. Surgery. 1994;116(2):285-92; discussion 292-3. PubMed PMID: 8047996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid modulation of liver-specific transcription factors after injury. AU - Burke,P A, AU - Drotar,M, AU - Luo,M, AU - Yaffe,M, AU - Forse,R A, PY - 1994/8/1/pubmed PY - 1994/8/1/medline PY - 1994/8/1/entrez SP - 285-92; discussion 292-3 JF - Surgery JO - Surgery VL - 116 IS - 2 N2 - BACKGROUND: The reaction to injury is a well-orchestrated physiologic response involving the coordinated actions of multiple integrated systems. It initially occurs at the molecular level and involves changes in gene transcription. We hypothesized that the molecular mechanisms regulating the generation of an inflammatory response are similar to those orchestrating developmental and tissue-specific expression of proteins and, in the case of the acute phase response, occur through manipulation of liver-specific transcription factors and their binding activity. METHODS: Female BALB/c mice, 7 to 8 weeks old, were subjected to a 15% body surface area burn. Total and polyadenylated liver RNA was isolated, and Northern blot analysis was performed to determine the kinetics of the acute phase proteins albumin and fibrinogen and the liver-specific transcriptional factors CCAAT-enhancer binding protein (C/EBP) alpha, hepatocyte nuclear factor (HNF)-1 alpha, and HNF-4. RESULTS: Induction of the injury response was shown by an increase in fibrinogen messenger RNA levels and a decrease in albumin mRNA levels. The liver-specific transcription factor C/EBP alpha decreased after injury and remained significantly lower than control at 3 hours. HNF-4 mRNA levels fell more slowly, reaching significantly lower levels at 6 hours and remaining suppressed at 34 hours. HNF-1 alpha showed the most rapid fall in mRNA levels at 30 minutes after injury and remained significantly below control levels at 34 hours. CONCLUSIONS: The minimal burn injury model leads to the molecular induction of the acute phase response and induces significant and rapid changes in the liver-specific transcription factors C/EBP alpha, HNF-1 alpha, and HNF-4. These changes may represent a mechanism through which the organ-specific response to injury is mediated. SN - 0039-6060 UR - https://www.unboundmedicine.com/medline/citation/8047996/Rapid_modulation_of_liver_specific_transcription_factors_after_injury_ L2 - https://medlineplus.gov/burns.html DB - PRIME DP - Unbound Medicine ER -