Tags

Type your tag names separated by a space and hit enter

Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in hepatic fibrosis of rat.
Regul Pept. 2007 Jan 10; 138(1):15-25.RP

Abstract

BACKGROUND/AIMS

Intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in the fibrogenesis of liver. However, the signal transduction mechanism underlying effects of Angiotensin II (Ang II) and Aldosterone (Aldo) on Nuclear Factor-kappaB (NF-kappaB) and active protein-1 (AP-1) pathway in hepatic fibrogenesis remains to be fully elucidated. The present study aims to investigate the signal transduction mechanism underlying effects of Ang II and Aldo on NF-kappaB and AP-1 pathway during hepatic fibrogenesis.

METHODS

To assess the effect of AECI and Angiotensin II type 1 receptor (AT-1 receptor) blocker on NF-kappaB activity in liver, a model of fibrosis was performed in rat. In vitro, hepatic stellate cells (HSCs)-T6 cells were preincubated for 1 h or not with U0126, a specific inhibitor of extracellular signal regulated kinase (ERK), irbesartan, and N-acetylcysteine prior to exposure to Ang II or Aldo for the indicated times. DNA binding activity of NF-kappaB and AP-1 were analyzed by Electrophoretic mobility shift assay (EMSA). Western blot was used to detect expression of IkappaBalpha and Phospho-P42/44. RT-PCR was used to detect the expressions of tumor necrosis factor alpha (TNFalpha) mRNA and alpha1 (I) procollagen mRNA.

RESULTS

AECI and AT-1 receptor blocker exert anti-fibrosis effect through inhibiting NF-kappaB activation in liver. Ang II and Aldo increase HSCs NF-kappaB activity and NF-kappaB target gene-TNFalpha expression by inhibiting IkappaBalpha expression in a redox-sensitive manner. Ang II and Aldo also markedly increase HSCs AP-1 activity and AP-1 target gene-alpha1 (I) procollagen mRNA expression via ERK1/2 pathway in a redox-sensitive manner.

CONCLUSIONS

These results show that stimulation of NF-kappaB and AP-1 pathway mediate hepatic fibrogenesis induced by intrahepatic RAAS.

Authors+Show Affiliations

Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. mylx99@163.comNo 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

16971004

Citation

Li, Xu, et al. "Angiotensin II and Aldosterone Stimulating NF-kappaB and AP-1 Activation in Hepatic Fibrosis of Rat." Regulatory Peptides, vol. 138, no. 1, 2007, pp. 15-25.
Li X, Meng Y, Wu P, et al. Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in hepatic fibrosis of rat. Regul Pept. 2007;138(1):15-25.
Li, X., Meng, Y., Wu, P., Zhang, Z., & Yang, X. (2007). Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in hepatic fibrosis of rat. Regulatory Peptides, 138(1), 15-25.
Li X, et al. Angiotensin II and Aldosterone Stimulating NF-kappaB and AP-1 Activation in Hepatic Fibrosis of Rat. Regul Pept. 2007 Jan 10;138(1):15-25. PubMed PMID: 16971004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II and Aldosterone stimulating NF-kappaB and AP-1 activation in hepatic fibrosis of rat. AU - Li,Xu, AU - Meng,Ying, AU - Wu,Pingsheng, AU - Zhang,Zhenshu, AU - Yang,Xishan, Y1 - 2006/09/12/ PY - 2005/12/23/received PY - 2006/07/20/revised PY - 2006/07/20/accepted PY - 2006/9/15/pubmed PY - 2007/5/15/medline PY - 2006/9/15/entrez SP - 15 EP - 25 JF - Regulatory peptides JO - Regul Pept VL - 138 IS - 1 N2 - BACKGROUND/AIMS: Intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in the fibrogenesis of liver. However, the signal transduction mechanism underlying effects of Angiotensin II (Ang II) and Aldosterone (Aldo) on Nuclear Factor-kappaB (NF-kappaB) and active protein-1 (AP-1) pathway in hepatic fibrogenesis remains to be fully elucidated. The present study aims to investigate the signal transduction mechanism underlying effects of Ang II and Aldo on NF-kappaB and AP-1 pathway during hepatic fibrogenesis. METHODS: To assess the effect of AECI and Angiotensin II type 1 receptor (AT-1 receptor) blocker on NF-kappaB activity in liver, a model of fibrosis was performed in rat. In vitro, hepatic stellate cells (HSCs)-T6 cells were preincubated for 1 h or not with U0126, a specific inhibitor of extracellular signal regulated kinase (ERK), irbesartan, and N-acetylcysteine prior to exposure to Ang II or Aldo for the indicated times. DNA binding activity of NF-kappaB and AP-1 were analyzed by Electrophoretic mobility shift assay (EMSA). Western blot was used to detect expression of IkappaBalpha and Phospho-P42/44. RT-PCR was used to detect the expressions of tumor necrosis factor alpha (TNFalpha) mRNA and alpha1 (I) procollagen mRNA. RESULTS: AECI and AT-1 receptor blocker exert anti-fibrosis effect through inhibiting NF-kappaB activation in liver. Ang II and Aldo increase HSCs NF-kappaB activity and NF-kappaB target gene-TNFalpha expression by inhibiting IkappaBalpha expression in a redox-sensitive manner. Ang II and Aldo also markedly increase HSCs AP-1 activity and AP-1 target gene-alpha1 (I) procollagen mRNA expression via ERK1/2 pathway in a redox-sensitive manner. CONCLUSIONS: These results show that stimulation of NF-kappaB and AP-1 pathway mediate hepatic fibrogenesis induced by intrahepatic RAAS. SN - 0167-0115 UR - https://www.unboundmedicine.com/medline/citation/16971004/Angiotensin_II_and_Aldosterone_stimulating_NF_kappaB_and_AP_1_activation_in_hepatic_fibrosis_of_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(06)00127-3 DB - PRIME DP - Unbound Medicine ER -