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Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α.

Publication ,  Journal Article
Bauzá, G; Miller, G; Kaseje, N; Wang, Z; Sherburne, A; Agarwal, S; Burke, PA
Published in: J Surg Res
June 15, 2012

BACKGROUND: The hepatic acute phase response(APR) is an organ-specific response to a diverse array of insults and is largely under transcriptional control. Liver-specific transcription factors, hepatic nuclear factors (HNFs)-1α and 4α play important roles in maintenance of liver phenotype and function and their binding activity changes early after injury. However, their roles in modulation of the liver's response over time are not defined. MATERIALS AND METHODS: C57/BL6 mice were anesthetized and exposed to 95°C water for 10 s to create a 15% body surface area full-thickness burn. At specific time points, the mice were sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for fibrinogen-γ and serum amyloid A(SAA)-3 were obtained through polymerase chain reaction (PCR). Transcriptional factor binding activity was assessed with electrophoretic mobility shift assays. RESULTS: Serum IL-6 levels peaked at 3 h and fibrinogen-γ and SAA mRNA levels increased more than 6-fold at 12 h before returning to control levels at 48 h. The binding activity of HNF-4α and HNF-1α rapidly declined after injury (1.5 h) but recovered to near control level at 24 and 6 h, respectively. CONCLUSIONS: Changes in HNF-4α and HNF-1α binding occurred before changes in acute phase protein mRNA levels and were preceded by the peak in IL-6 levels. The rapid suppression and reconstitution of liver-specific transcription factor binding after injury may represent a mechanism that allows the normal liver phenotype to change and an injury-response phenotype to prevail. This mechanism in the liver's adaptive response to injury suggests a central role for both HNF-4α and HNF-1α in transcriptional regulation of the hepatic APR.

Duke Scholars

Published In

J Surg Res

DOI

EISSN

1095-8673

Publication Date

June 15, 2012

Volume

175

Issue

2

Start / End Page

298 / 304

Location

United States

Related Subject Headings

  • Surgery
  • Serum Amyloid A Protein
  • RNA, Messenger
  • Models, Animal
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver
  • Interleukin-6
  • Hepatocyte Nuclear Factor 4
 

Citation

APA
Chicago
ICMJE
MLA
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Bauzá, G., Miller, G., Kaseje, N., Wang, Z., Sherburne, A., Agarwal, S., & Burke, P. A. (2012). Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α. J Surg Res, 175(2), 298–304. https://doi.org/10.1016/j.jss.2011.04.062
Bauzá, Graciela, Glenn Miller, Neema Kaseje, Zhongyan Wang, Alan Sherburne, Suresh Agarwal, and Peter A. Burke. “Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α.J Surg Res 175, no. 2 (June 15, 2012): 298–304. https://doi.org/10.1016/j.jss.2011.04.062.
Bauzá G, Miller G, Kaseje N, Wang Z, Sherburne A, Agarwal S, et al. Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α. J Surg Res. 2012 Jun 15;175(2):298–304.
Bauzá, Graciela, et al. “Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α.J Surg Res, vol. 175, no. 2, June 2012, pp. 298–304. Pubmed, doi:10.1016/j.jss.2011.04.062.
Bauzá G, Miller G, Kaseje N, Wang Z, Sherburne A, Agarwal S, Burke PA. Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α. J Surg Res. 2012 Jun 15;175(2):298–304.
Journal cover image

Published In

J Surg Res

DOI

EISSN

1095-8673

Publication Date

June 15, 2012

Volume

175

Issue

2

Start / End Page

298 / 304

Location

United States

Related Subject Headings

  • Surgery
  • Serum Amyloid A Protein
  • RNA, Messenger
  • Models, Animal
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver
  • Interleukin-6
  • Hepatocyte Nuclear Factor 4