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[Angiotensin II and aldosterone stimulate alpha1-(I) procollagen mRNA expression in hepatic stellate cells via activation of ERK1/2 and AP-1].
Zhonghua Yi Xue Za Zhi. 2005 Jul 13; 85(26):1831-5.ZY

Abstract

OBJECTIVE

To investigate the signal transduction mechanism underlying the effects of angiotensin II (Ang II) and aldosterone (Aldo) on the signal passageway of active protein-1 (AP-1).

METHODS

In vitro, Hepatic stellate cells (HSCs) of the line HSC-T6 were cultured and treated with Ang II or Aldo, the principal effector molecules of the renin-angiotensin-aldosterone system (RAAS) for 10, 30, 60, 120, and 180 minutes respectively. The protein expression of phospho-P42/44 was detected by Western blotting. In addition, HSC-T6 cells were preincubated for 60 min with U0126, an inhibitor of MAPK/ERK kinase, irbesartan, an AT-1 receptor blocker, N-acetylcysteine (NAC), antioxidant, angiotensin converting enzyme inhibitor (ACEI), or tumor necrosis factor alpha (TNFalpha) prior to exposure to Ang II or Aldo. Then the protein expression of phospho-P42/44 was measured by Western blotting. The DNA biding activity of AP-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of RT-PCR, the mRNA expression of alpha1 (I) procollagen was detected.

RESULTS

The levels of phopho-ERK1/2 protein increased after the treatment of Ang II and Aldo at all time points and both peaked 10 minutes after (both P < 0.01). The levels of phopho-ERK1/2 protein of the irbesartan + Ang II and U0126 + Ang II groups were significantly lower than that of the Ang II group (both P < 0.01). The level of phopho-ERK1/2 protein of the Ang II group was lower than that of the TNFalpha group, however, was especially significantly lower than that of the Ang II + TNFalpha group (P < 0.01). The level of phopho-ERK1/2 protein of the U0126 + Aldo group was significantly lower than that of the Aldo group (P < 0.01). The phopho-ERK1/2 protein level of the NAC + Aldo group was not significantly different from that of the Aldo group (P > 0.05). The phopho-ERK1/2 protein level of the Aldo group was lower than that of the TNFalpha group, however, was especially significantly lower than that of the Aldo + TNFalpha group (P < 0.01). The AP-1 DNA binding protein increased after the treatment of Ang II and peaked 30 min after. U0126, irbesartan, and NAC, as well as ACEUI, significantly inhibited the increased AP-1 DNA binding activity induced by Ang II. The AP-1 DNA binding protein increased after the treatment of Aldo and peaked twice, 30 min and 240 min after. U0126 and NAC significantly and NAC partly inhibited the increased AP-1 DNA binding activity induced by Aldo.

CONCLUSION

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

Authors+Show Affiliations

Institute for Digestive Diseases, Nanfang Hospital, Nanfang Medical University, Guangzhou 510515, China.No affiliation info availableNo 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

16253189

Citation

Li, Xu, et al. "[Angiotensin II and Aldosterone Stimulate alpha1-(I) Procollagen mRNA Expression in Hepatic Stellate Cells Via Activation of ERK1/2 and AP-1]." Zhonghua Yi Xue Za Zhi, vol. 85, no. 26, 2005, pp. 1831-5.
Li X, Meng Y, Cai SX, et al. [Angiotensin II and aldosterone stimulate alpha1-(I) procollagen mRNA expression in hepatic stellate cells via activation of ERK1/2 and AP-1]. Zhonghua Yi Xue Za Zhi. 2005;85(26):1831-5.
Li, X., Meng, Y., Cai, S. X., Yang, X. S., Zhang, Y. J., & Wu, P. S. (2005). [Angiotensin II and aldosterone stimulate alpha1-(I) procollagen mRNA expression in hepatic stellate cells via activation of ERK1/2 and AP-1]. Zhonghua Yi Xue Za Zhi, 85(26), 1831-5.
Li X, et al. [Angiotensin II and Aldosterone Stimulate alpha1-(I) Procollagen mRNA Expression in Hepatic Stellate Cells Via Activation of ERK1/2 and AP-1]. Zhonghua Yi Xue Za Zhi. 2005 Jul 13;85(26):1831-5. PubMed PMID: 16253189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Angiotensin II and aldosterone stimulate alpha1-(I) procollagen mRNA expression in hepatic stellate cells via activation of ERK1/2 and AP-1]. AU - Li,Xu, AU - Meng,Ying, AU - Cai,Shao-xi, AU - Yang,Xi-shan, AU - Zhang,Yi-jun, AU - Wu,Ping-sheng, PY - 2005/10/29/pubmed PY - 2014/1/24/medline PY - 2005/10/29/entrez SP - 1831 EP - 5 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 85 IS - 26 N2 - OBJECTIVE: To investigate the signal transduction mechanism underlying the effects of angiotensin II (Ang II) and aldosterone (Aldo) on the signal passageway of active protein-1 (AP-1). METHODS: In vitro, Hepatic stellate cells (HSCs) of the line HSC-T6 were cultured and treated with Ang II or Aldo, the principal effector molecules of the renin-angiotensin-aldosterone system (RAAS) for 10, 30, 60, 120, and 180 minutes respectively. The protein expression of phospho-P42/44 was detected by Western blotting. In addition, HSC-T6 cells were preincubated for 60 min with U0126, an inhibitor of MAPK/ERK kinase, irbesartan, an AT-1 receptor blocker, N-acetylcysteine (NAC), antioxidant, angiotensin converting enzyme inhibitor (ACEI), or tumor necrosis factor alpha (TNFalpha) prior to exposure to Ang II or Aldo. Then the protein expression of phospho-P42/44 was measured by Western blotting. The DNA biding activity of AP-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of RT-PCR, the mRNA expression of alpha1 (I) procollagen was detected. RESULTS: The levels of phopho-ERK1/2 protein increased after the treatment of Ang II and Aldo at all time points and both peaked 10 minutes after (both P < 0.01). The levels of phopho-ERK1/2 protein of the irbesartan + Ang II and U0126 + Ang II groups were significantly lower than that of the Ang II group (both P < 0.01). The level of phopho-ERK1/2 protein of the Ang II group was lower than that of the TNFalpha group, however, was especially significantly lower than that of the Ang II + TNFalpha group (P < 0.01). The level of phopho-ERK1/2 protein of the U0126 + Aldo group was significantly lower than that of the Aldo group (P < 0.01). The phopho-ERK1/2 protein level of the NAC + Aldo group was not significantly different from that of the Aldo group (P > 0.05). The phopho-ERK1/2 protein level of the Aldo group was lower than that of the TNFalpha group, however, was especially significantly lower than that of the Aldo + TNFalpha group (P < 0.01). The AP-1 DNA binding protein increased after the treatment of Ang II and peaked 30 min after. U0126, irbesartan, and NAC, as well as ACEUI, significantly inhibited the increased AP-1 DNA binding activity induced by Ang II. The AP-1 DNA binding protein increased after the treatment of Aldo and peaked twice, 30 min and 240 min after. U0126 and NAC significantly and NAC partly inhibited the increased AP-1 DNA binding activity induced by Aldo. CONCLUSION: Stimulation of HSC by Ang II and Aldo results in activation of AP-1 via ERK1/2 pathway leading to up-regulation of AP-1 target gene alpha1 (I) procollagen mRNA expression. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/16253189/[Angiotensin_II_and_aldosterone_stimulate_alpha1__I__procollagen_mRNA_expression_in_hepatic_stellate_cells_via_activation_of_ERK1/2_and_AP_1]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2005&amp;vol=85&amp;issue=26&amp;fpage=1831 DB - PRIME DP - Unbound Medicine ER -