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[Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1].
Zhonghua Gan Zang Bing Za Zhi. 2005 Nov; 13(11):815-8.ZG

Abstract

OBJECTIVE

It has been known that the intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in the fibrogenesis in livers. Aldosterone (Aldo), the principal effector molecule of the RAAS, exerts local effects on cell growth and fibrogenesis. However, the signal transduction mechanisms underlying the effects of Aldo on hepatic fibrogenesis remain to be fully elucidated. The present study aims to investigate the signal transduction mechanism underlying the effects of Aldo on the signal passageway of active protein-1 (AP-1).

METHODS

In vitro, HSCs-T6 cell line was treated with Aldo for 10 min, 30 min, 60 min, 120 min and 180 min, and protein expression of Phospho-P42/44 was detected by Western blot. In addition, HSCs-T6 cell line was preincubated for 60 min or not with U0126 (an inhibitor of the MAPK/ERK kinase), and also with antioxidant-N-acetylcysteine (NAC) prior to exposure to Aldo for the indicated times. Protein expression of Phospho-P42/44 was measured by Western blot. DNA biding activity of AP-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of RT-PCR, expression of alpha1(1) procollagen mRNA was detected.

RESULTS

Aldo stimulated HSC via extracellular signal-regulated kinase (ERK1/2) pathway. Time course experiments showed that Aldo induced Phospho-P42/44 expression, which was abrogated by U0126, reaching a maximum at 10 minutes, and then declined progressively. NAC inhibited the Phospho-P42/44 expression. EMSA showed that stimulation of HSC by Aldo markedly increased AP-1 DNA binding activity. U0126 markedly reduced AP-1 DNA binding activity induced by Aldo; NAC partly decreased AP-1 activity induced by Aldo. Aldo up-regulated expression of alpha1(1) procollagen mRNA, which was attenuated by U0126 and NAC.

CONCLUSION

Stimulation of HSC by Aldo results in activation of AP-1 via ERK1/2 pathway, leading to up-regulation of AP-1 target gene alpha1(1) procollagen mRNA expression.

Authors+Show Affiliations

Emergency Department, Nanfang Hospital, Nanfang 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

chi

PubMed ID

16313723

Citation

Li, Xu, et al. "[Aldosterone Stimulates Alpha1-(1) Procollagen mRNA Expression in HSC Via Activation of ERK1/2 and AP-1]." Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, vol. 13, no. 11, 2005, pp. 815-8.
Li X, Meng Y, Cai SX, et al. [Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1]. Zhonghua Gan Zang Bing Za Zhi. 2005;13(11):815-8.
Li, X., Meng, Y., Cai, S. X., Yang, X. S., & Wu, P. S. (2005). [Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1]. Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 13(11), 815-8.
Li X, et al. [Aldosterone Stimulates Alpha1-(1) Procollagen mRNA Expression in HSC Via Activation of ERK1/2 and AP-1]. Zhonghua Gan Zang Bing Za Zhi. 2005;13(11):815-8. PubMed PMID: 16313723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Aldosterone stimulates alpha1-(1) procollagen mRNA expression in HSC via activation of ERK1/2 and AP-1]. AU - Li,Xu, AU - Meng,Ying, AU - Cai,Shao-xi, AU - Yang,Xi-shan, AU - Wu,Ping-sheng, PY - 2005/11/30/pubmed PY - 2007/8/29/medline PY - 2005/11/30/entrez SP - 815 EP - 8 JF - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JO - Zhonghua Gan Zang Bing Za Zhi VL - 13 IS - 11 N2 - OBJECTIVE: It has been known that the intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in the fibrogenesis in livers. Aldosterone (Aldo), the principal effector molecule of the RAAS, exerts local effects on cell growth and fibrogenesis. However, the signal transduction mechanisms underlying the effects of Aldo on hepatic fibrogenesis remain to be fully elucidated. The present study aims to investigate the signal transduction mechanism underlying the effects of Aldo on the signal passageway of active protein-1 (AP-1). METHODS: In vitro, HSCs-T6 cell line was treated with Aldo for 10 min, 30 min, 60 min, 120 min and 180 min, and protein expression of Phospho-P42/44 was detected by Western blot. In addition, HSCs-T6 cell line was preincubated for 60 min or not with U0126 (an inhibitor of the MAPK/ERK kinase), and also with antioxidant-N-acetylcysteine (NAC) prior to exposure to Aldo for the indicated times. Protein expression of Phospho-P42/44 was measured by Western blot. DNA biding activity of AP-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of RT-PCR, expression of alpha1(1) procollagen mRNA was detected. RESULTS: Aldo stimulated HSC via extracellular signal-regulated kinase (ERK1/2) pathway. Time course experiments showed that Aldo induced Phospho-P42/44 expression, which was abrogated by U0126, reaching a maximum at 10 minutes, and then declined progressively. NAC inhibited the Phospho-P42/44 expression. EMSA showed that stimulation of HSC by Aldo markedly increased AP-1 DNA binding activity. U0126 markedly reduced AP-1 DNA binding activity induced by Aldo; NAC partly decreased AP-1 activity induced by Aldo. Aldo up-regulated expression of alpha1(1) procollagen mRNA, which was attenuated by U0126 and NAC. CONCLUSION: Stimulation of HSC by Aldo results in activation of AP-1 via ERK1/2 pathway, leading to up-regulation of AP-1 target gene alpha1(1) procollagen mRNA expression. SN - 1007-3418 UR - https://www.unboundmedicine.com/medline/citation/16313723/[Aldosterone_stimulates_alpha1__1__procollagen_mRNA_expression_in_HSC_via_activation_of_ERK1/2_and_AP_1]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=1007-3418&year=2005&vol=13&issue=11&fpage=815 DB - PRIME DP - Unbound Medicine ER -