Increased DNA binding activity of NF-kappaB, STAT-3, SMAD3 and AP-1 in acutely damaged liver.
OBJECTIVE
To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration.


METHODS
USING gel-shift assay and RT-PCR, transcription factors, such as NF-kappaB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy.


RESULTS
Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl(4) intoxi-cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-kappaB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post-intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times.


CONCLUSIONS
TNF-alpha and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.
Salazar-Montes
Adriana
A
Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Apdo. Postal 2-123, Guadalajara 44281, Jal, Mexico. adriana.salazar@cucs.udg.mx
Ruiz-Corro
Luis
L
Sandoval-Rodriguez
Ana
A
Lopez-Reyes
Alberto
A
Armendariz-Borunda
Juan
J
D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects / Q000494:pharmacology; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C494088:Stat3 protein, rat; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor; D004247:DNA; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019859:Proto-Oncogene Proteins c-met