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[Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1].
Zhonghua Gan Zang Bing Za Zhi. 2005 Aug; 13(8):567-70.ZG

Abstract

OBJECTIVE

It is known that intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in liver fibrogenesis. 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 extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response-1 (EGR-1) and on the platelet-derived growth factor-B (PDGF-B).

METHODS

In vitro, hepatic stellate cell (HSC)-T6 cell line was treated with Aldo for 10 min, 0.5 h, 1 h, 2 h and 3 h. Protein expression of phospho-p42/44 was detected by Western blot. In addition, HSC-T6 were preincubated for 1 h or not at all with U0126 (an inhibitor of the MAPK/ERK kinase), and antioxidant-N-acetylcysteine (NAC) prior to exposure to Aldo for the indicated times. Protein expressions of phospho-p42/44 and PDGF-B were measured by Western blot. DNA biding activity of EGR-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of immunohistochemistry, expression of PDGF-B was detected.

RESULTS

Aldo induced phospho-p42/44 expression could be abrogated by U0126; NAC did not inhibit phospho-p42/44 expression. Gel shift study showed that stimulation of HSC by Aldo markedly increased the EGR-1 DNA binding activity, which was abrogated by U0126, reaching a maximum at 60 minutes, and then declined progressively. NAC did not reduce the EGR-1 activity. Aldo increased the PDGF-B protein level in HSC, which was not attenuated by NAC and U0126.

CONCLUSIONS

Stimulation of HSC by Aldo results in activation of EGR-1 via ERK1/2 pathway, leading to up-regulation of PDGF-B 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)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

16092976

Citation

Li, Xu, et al. "[Aldosterone Stimulating PDGF-B Expression in HSC Via Activation of EGR-1]." Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, vol. 13, no. 8, 2005, pp. 567-70.
Li X, Meng Y, Yang XS, et al. [Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1]. Zhonghua Gan Zang Bing Za Zhi. 2005;13(8):567-70.
Li, X., Meng, Y., Yang, X. S., Wu, P. S., & Zhang, Z. S. (2005). [Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1]. Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 13(8), 567-70.
Li X, et al. [Aldosterone Stimulating PDGF-B Expression in HSC Via Activation of EGR-1]. Zhonghua Gan Zang Bing Za Zhi. 2005;13(8):567-70. PubMed PMID: 16092976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1]. AU - Li,Xu, AU - Meng,Ying, AU - Yang,Xi-shan, AU - Wu,Ping-sheng, AU - Zhang,Zhen-shu, PY - 2005/8/12/pubmed PY - 2007/8/24/medline PY - 2005/8/12/entrez SP - 567 EP - 70 JF - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JO - Zhonghua Gan Zang Bing Za Zhi VL - 13 IS - 8 N2 - OBJECTIVE: It is known that intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in liver fibrogenesis. 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 extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response-1 (EGR-1) and on the platelet-derived growth factor-B (PDGF-B). METHODS: In vitro, hepatic stellate cell (HSC)-T6 cell line was treated with Aldo for 10 min, 0.5 h, 1 h, 2 h and 3 h. Protein expression of phospho-p42/44 was detected by Western blot. In addition, HSC-T6 were preincubated for 1 h or not at all with U0126 (an inhibitor of the MAPK/ERK kinase), and antioxidant-N-acetylcysteine (NAC) prior to exposure to Aldo for the indicated times. Protein expressions of phospho-p42/44 and PDGF-B were measured by Western blot. DNA biding activity of EGR-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of immunohistochemistry, expression of PDGF-B was detected. RESULTS: Aldo induced phospho-p42/44 expression could be abrogated by U0126; NAC did not inhibit phospho-p42/44 expression. Gel shift study showed that stimulation of HSC by Aldo markedly increased the EGR-1 DNA binding activity, which was abrogated by U0126, reaching a maximum at 60 minutes, and then declined progressively. NAC did not reduce the EGR-1 activity. Aldo increased the PDGF-B protein level in HSC, which was not attenuated by NAC and U0126. CONCLUSIONS: Stimulation of HSC by Aldo results in activation of EGR-1 via ERK1/2 pathway, leading to up-regulation of PDGF-B expression. SN - 1007-3418 UR - https://www.unboundmedicine.com/medline/citation/16092976/[Aldosterone_stimulating_PDGF_B_expression_in_HSC_via_activation_of_EGR_1]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=1007-3418&year=2005&vol=13&issue=8&fpage=567 DB - PRIME DP - Unbound Medicine ER -