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[Activating protein-1 complex regulates oxidized low density lipoprotein-induced overproduction of rat TGF-beta1 at transcriptional level].
Zhonghua Yi Xue Za Zhi. 2002 Oct 10; 82(19):1346-50.ZY

Abstract

OBJECTIVE

To clarify whether the activating protein-1 (AP-1) is involved in the transcriptional regulation of expression of oxidized low density lipoprotein (Ox-LDL) induced transforming growth factor (TGF)-beta(1) gene and further to investigate the possible signal transduction pathway in the cultured mesangial cells (MsCs).

METHODS

Firstly, a deletion analysis of SD rat renal mesangial TGF-beta(1) promoter (pRT)--luciferase reporter genes was adopted to identify the possible regulatory regions responding to Ox-LDL. With mutation of AP-1 binding site and addition of the c-Jun/AP-1 inhibitor curcumin, the changes of relative luciferase of pRT stimulated by Ox-LDL were assayed, respectively. Furthermore, the phosphorylation of p38MAPK was detected by Western blotting. Pre-treatment with the different specific kinase inhibitors, the activities of AP-1 induced by Ox-LDL were determined by electrophoretic mobility shift assay (EMSA).

RESULTS

Relative luciferase activity showed two regions responding to stimulation by Ox-LDL in rat TGF-beta(1) promoter: one positive regulatory region (-1 550 to -845) containing an accurate AP-1 binding site, and one negative (-629 to -422) regulatory region. Both mutation of AP-1 binding site and addition of curcumin markedly decrease of activity of TGF-beta(1) promoter. The phosphorylation, but not total protein, of p38MAPK was significantly enhanced by Ox-LDL stimulation. The inhibitor of PKC remarkably reduced the activity of AP-1 induced by Ox-LDL. Reversely, the activity of AP-1 didn't significantly change with the inhibitor of p38MAPK.

CONCLUSION

In the cultured rat mesangial cells, the AP-1 complex regulates Ox-LDL induced-overproduction of TGF-beta(1) at the transcriptional level. Furthermore, the functional and structural results showed that Ox-LDL regulates rat TGF-beta(1) gene expression through AP-1 binding site and c-Jun/AP-1 complex, it gives rise to the involvement of protein kinase C, but not p38MAPK, in Ox-LDL-induced TGF-beta(1) gene expression.

Authors+Show Affiliations

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.No 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

12509941

Citation

Zhou, Qin, et al. "[Activating Protein-1 Complex Regulates Oxidized Low Density Lipoprotein-induced Overproduction of Rat TGF-beta1 at Transcriptional Level]." Zhonghua Yi Xue Za Zhi, vol. 82, no. 19, 2002, pp. 1346-50.
Zhou Q, Lan Y, Wang Y, et al. [Activating protein-1 complex regulates oxidized low density lipoprotein-induced overproduction of rat TGF-beta1 at transcriptional level]. Zhonghua Yi Xue Za Zhi. 2002;82(19):1346-50.
Zhou, Q., Lan, Y., Wang, Y., Zhao, Y., & Wu, Z. (2002). [Activating protein-1 complex regulates oxidized low density lipoprotein-induced overproduction of rat TGF-beta1 at transcriptional level]. Zhonghua Yi Xue Za Zhi, 82(19), 1346-50.
Zhou Q, et al. [Activating Protein-1 Complex Regulates Oxidized Low Density Lipoprotein-induced Overproduction of Rat TGF-beta1 at Transcriptional Level]. Zhonghua Yi Xue Za Zhi. 2002 Oct 10;82(19):1346-50. PubMed PMID: 12509941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Activating protein-1 complex regulates oxidized low density lipoprotein-induced overproduction of rat TGF-beta1 at transcriptional level]. AU - Zhou,Qin, AU - Lan,Yang, AU - Wang,Yuancheng, AU - Zhao,Yun, AU - Wu,Zhaolong, PY - 2003/1/3/pubmed PY - 2003/8/2/medline PY - 2003/1/3/entrez SP - 1346 EP - 50 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 82 IS - 19 N2 - OBJECTIVE: To clarify whether the activating protein-1 (AP-1) is involved in the transcriptional regulation of expression of oxidized low density lipoprotein (Ox-LDL) induced transforming growth factor (TGF)-beta(1) gene and further to investigate the possible signal transduction pathway in the cultured mesangial cells (MsCs). METHODS: Firstly, a deletion analysis of SD rat renal mesangial TGF-beta(1) promoter (pRT)--luciferase reporter genes was adopted to identify the possible regulatory regions responding to Ox-LDL. With mutation of AP-1 binding site and addition of the c-Jun/AP-1 inhibitor curcumin, the changes of relative luciferase of pRT stimulated by Ox-LDL were assayed, respectively. Furthermore, the phosphorylation of p38MAPK was detected by Western blotting. Pre-treatment with the different specific kinase inhibitors, the activities of AP-1 induced by Ox-LDL were determined by electrophoretic mobility shift assay (EMSA). RESULTS: Relative luciferase activity showed two regions responding to stimulation by Ox-LDL in rat TGF-beta(1) promoter: one positive regulatory region (-1 550 to -845) containing an accurate AP-1 binding site, and one negative (-629 to -422) regulatory region. Both mutation of AP-1 binding site and addition of curcumin markedly decrease of activity of TGF-beta(1) promoter. The phosphorylation, but not total protein, of p38MAPK was significantly enhanced by Ox-LDL stimulation. The inhibitor of PKC remarkably reduced the activity of AP-1 induced by Ox-LDL. Reversely, the activity of AP-1 didn't significantly change with the inhibitor of p38MAPK. CONCLUSION: In the cultured rat mesangial cells, the AP-1 complex regulates Ox-LDL induced-overproduction of TGF-beta(1) at the transcriptional level. Furthermore, the functional and structural results showed that Ox-LDL regulates rat TGF-beta(1) gene expression through AP-1 binding site and c-Jun/AP-1 complex, it gives rise to the involvement of protein kinase C, but not p38MAPK, in Ox-LDL-induced TGF-beta(1) gene expression. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/12509941/[Activating_protein_1_complex_regulates_oxidized_low_density_lipoprotein_induced_overproduction_of_rat_TGF_beta1_at_transcriptional_level]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=0376-2491&year=2002&vol=82&issue=19&fpage=1346 DB - PRIME DP - Unbound Medicine ER -