Increased DNA binding activity of NF-kappaB, STAT-3, SMAD3 and AP-1 in acutely damaged liver

• Published in: World journal of gastroenterology : WJG 2006-10, Vol.12 (37), p.5995
• Main Authors: Salazar-Montes, Adriana, Ruiz-Corro, Luis, Sandoval-Rodriguez, Ana, Lopez-Reyes, Alberto, Armendariz-Borunda, Juan
• Format: Article
• Language: English
• Subjects: Animals; Carbon Tetrachloride - adverse effects; Carbon Tetrachloride - pharmacology; Cell Proliferation; DNA - genetics; DNA - metabolism; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Hepatectomy; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Regeneration - genetics; Liver Regeneration - physiology; Male; NF-kappa B - genetics; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Rats; Rats, Wistar; Smad3 Protein - genetics; Smad3 Protein - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1007-9327

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. 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. 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. 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.