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Transcription factor AP-1 regulates TGF-beta(1)-induced expression of aldose reductase in cultured human mesangial cells.
Nephrology (Carlton). 2008 Jun; 13(3):212-7.N

Abstract

AIM

The previous studies demonstrated that transforming growth factor-beta(1) (TGF-beta(1)) could upregulate the expression of aldose reductase (AR). The aim of this study is to clarify (investigate) the mechanism of TGF-beta(1)-induced AR expression.

METHODS

Real-time polymerase chain reaction and western blot were used to analyse the AR expression in mRNA and protein levels in human mesangial cells, and reporter assay was used to analyse the function of various sites within 5'-flanking region of AR gene in AR expression.

RESULTS

TGF-beta(1) (4 ng/mL) stimulation could upregulate AR expression. The cells pretreated with pharmacological inhibitors, U0126 and PD98059 for blocking extracellular signal-related kinase (ERK) signalling pathway or SP6000125 for blocking c-Jun N-terminal kinase (JNK) signalling pathway, respectively, showed reduced expression of AR after TGF-beta(1) stimulation. Similarly, the cells transiently transfected with pCMVTAM67, which is an expression plasmid for DN-c-Jun showed decreasing AR expression. Reporter assay revealed that the 5'-promoter region of AR consisting of an AP-1 site and two putative antioxidant response elements (ARE) was responsible for TGF-beta(1) stimulation. Mutation of either ARE did not affect the promoter activity in the reporter assay while mutation of AP-1 site caused a significant decrease in the responsiveness to TGF-beta(1).

CONCLUSION

TGF-beta(1) upregulate AR expression in both mRNA and protein levels. The results demonstrated that ERK and JNK are involved in the downstream signalling pathways and transcription factor AP-1 plays an important role in the regulation of TGF-beta(1)-induced AR expression in mesangial cells.

Authors+Show Affiliations

Department of Pathology, Shanghai Medical School, Fudan University, Shanghai, China.No 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

18315703

Citation

Jiang, Tao, et al. "Transcription Factor AP-1 Regulates TGF-beta(1)-induced Expression of Aldose Reductase in Cultured Human Mesangial Cells." Nephrology (Carlton, Vic.), vol. 13, no. 3, 2008, pp. 212-7.
Jiang T, Qu JJ, Nishinaka T, et al. Transcription factor AP-1 regulates TGF-beta(1)-induced expression of aldose reductase in cultured human mesangial cells. Nephrology (Carlton). 2008;13(3):212-7.
Jiang, T., Qu, J. J., Nishinaka, T., & Zhang, N. (2008). Transcription factor AP-1 regulates TGF-beta(1)-induced expression of aldose reductase in cultured human mesangial cells. Nephrology (Carlton, Vic.), 13(3), 212-7. https://doi.org/10.1111/j.1440-1797.2007.00913.x
Jiang T, et al. Transcription Factor AP-1 Regulates TGF-beta(1)-induced Expression of Aldose Reductase in Cultured Human Mesangial Cells. Nephrology (Carlton). 2008;13(3):212-7. PubMed PMID: 18315703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription factor AP-1 regulates TGF-beta(1)-induced expression of aldose reductase in cultured human mesangial cells. AU - Jiang,Tao, AU - Qu,Jie J, AU - Nishinaka,Toru, AU - Zhang,Nong, PY - 2008/3/5/pubmed PY - 2008/4/19/medline PY - 2008/3/5/entrez SP - 212 EP - 7 JF - Nephrology (Carlton, Vic.) JO - Nephrology (Carlton) VL - 13 IS - 3 N2 - AIM: The previous studies demonstrated that transforming growth factor-beta(1) (TGF-beta(1)) could upregulate the expression of aldose reductase (AR). The aim of this study is to clarify (investigate) the mechanism of TGF-beta(1)-induced AR expression. METHODS: Real-time polymerase chain reaction and western blot were used to analyse the AR expression in mRNA and protein levels in human mesangial cells, and reporter assay was used to analyse the function of various sites within 5'-flanking region of AR gene in AR expression. RESULTS: TGF-beta(1) (4 ng/mL) stimulation could upregulate AR expression. The cells pretreated with pharmacological inhibitors, U0126 and PD98059 for blocking extracellular signal-related kinase (ERK) signalling pathway or SP6000125 for blocking c-Jun N-terminal kinase (JNK) signalling pathway, respectively, showed reduced expression of AR after TGF-beta(1) stimulation. Similarly, the cells transiently transfected with pCMVTAM67, which is an expression plasmid for DN-c-Jun showed decreasing AR expression. Reporter assay revealed that the 5'-promoter region of AR consisting of an AP-1 site and two putative antioxidant response elements (ARE) was responsible for TGF-beta(1) stimulation. Mutation of either ARE did not affect the promoter activity in the reporter assay while mutation of AP-1 site caused a significant decrease in the responsiveness to TGF-beta(1). CONCLUSION: TGF-beta(1) upregulate AR expression in both mRNA and protein levels. The results demonstrated that ERK and JNK are involved in the downstream signalling pathways and transcription factor AP-1 plays an important role in the regulation of TGF-beta(1)-induced AR expression in mesangial cells. SN - 1440-1797 UR - https://www.unboundmedicine.com/medline/citation/18315703/Transcription_factor_AP_1_regulates_TGF_beta_1__induced_expression_of_aldose_reductase_in_cultured_human_mesangial_cells_ L2 - https://doi.org/10.1111/j.1440-1797.2007.00913.x DB - PRIME DP - Unbound Medicine ER -