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P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells.
Acta Pharmacol Sin. 2014 Sep; 35(9):1157-66.AP

Abstract

AIM

To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular epithelial cells.

METHODS

Rat renal tubular epithelial cell line (NRK-52E) was used. STAT3 acetylation and phosphorylation, as well as the expression of fibronectin, collagen IV and transforming growth factor-β1 (TGF-β1) were examined using Western blotting. The level and localization of STAT3 phosphorylation on Tyr705 were detected with fluorescence immunocytochemistry. The cells were transfected with a plasmid vector carrying p300 gene or siRNA targeting p300 to regulate p300 expression.

RESULTS

Overexpression of p300 significantly increased STAT3 acetylation on Lys685, STAT3 phosphorylation on Tyr705, and the expression of TGF-β1, collagen IV and fibronectin in the cells. Treatment of the cells with Ang II (1 μmol/L) significantly increased STAT3 phosphorylation on Tyr705 through JAK2 activation, and dose-dependently increased the expression of fibronectin, collagen IV and TGF-β1. Pretreatment with curcumin, an inhibitor of JAK2 and p300, blocked Ang II-induced effects. Knockdown of p300 significantly decreased STAT3 acetylation on Lys685, and abolished Ang II-stimulated STAT3 phosphorylation on Tyr705, whereas pretreatment of the cells with C646, a selective inhibitor of p300, inhibited Ang II-induced STAT3 nuclear translocation and the expression of TGF-β1, collagen IV and fibronectin. Pretreatment of the cells with AG490, a JAK2 inhibitor, markedly inhibited Ang II-induced STAT3 phosphorylation on Tyr705 and fibronectin expression.

CONCLUSION

p300-dependent STAT3 acetylation is necessary for Ang II-induced STAT3 phosphorylation and the consequent pro-fibrotic responses in renal tubular epithelial cells in vitro.

Authors+Show Affiliations

Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.School of Biomedical Sciences and Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Pub Type(s)

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

Language

eng

PubMed ID

25088002

Citation

Ni, Jun, et al. "P300-dependent STAT3 Acetylation Is Necessary for Angiotensin II-induced Pro-fibrotic Responses in Renal Tubular Epithelial Cells." Acta Pharmacologica Sinica, vol. 35, no. 9, 2014, pp. 1157-66.
Ni J, Shen Y, Wang Z, et al. P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells. Acta Pharmacol Sin. 2014;35(9):1157-66.
Ni, J., Shen, Y., Wang, Z., Shao, D. C., Liu, J., Kong, Y. L., Fu, L. J., Zhou, L., Xue, H., Huang, Y., Zhang, W., Yu, C., & Lu, L. M. (2014). P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells. Acta Pharmacologica Sinica, 35(9), 1157-66. https://doi.org/10.1038/aps.2014.54
Ni J, et al. P300-dependent STAT3 Acetylation Is Necessary for Angiotensin II-induced Pro-fibrotic Responses in Renal Tubular Epithelial Cells. Acta Pharmacol Sin. 2014;35(9):1157-66. PubMed PMID: 25088002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells. AU - Ni,Jun, AU - Shen,Yang, AU - Wang,Zhen, AU - Shao,De-cui, AU - Liu,Jia, AU - Kong,Ya-li, AU - Fu,Lan-jun, AU - Zhou,Li, AU - Xue,Hong, AU - Huang,Yu, AU - Zhang,Wei, AU - Yu,Chen, AU - Lu,Li-min, Y1 - 2014/08/04/ PY - 2014/03/28/received PY - 2014/05/20/accepted PY - 2014/8/5/entrez PY - 2014/8/5/pubmed PY - 2015/9/4/medline SP - 1157 EP - 66 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 35 IS - 9 N2 - AIM: To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular epithelial cells. METHODS: Rat renal tubular epithelial cell line (NRK-52E) was used. STAT3 acetylation and phosphorylation, as well as the expression of fibronectin, collagen IV and transforming growth factor-β1 (TGF-β1) were examined using Western blotting. The level and localization of STAT3 phosphorylation on Tyr705 were detected with fluorescence immunocytochemistry. The cells were transfected with a plasmid vector carrying p300 gene or siRNA targeting p300 to regulate p300 expression. RESULTS: Overexpression of p300 significantly increased STAT3 acetylation on Lys685, STAT3 phosphorylation on Tyr705, and the expression of TGF-β1, collagen IV and fibronectin in the cells. Treatment of the cells with Ang II (1 μmol/L) significantly increased STAT3 phosphorylation on Tyr705 through JAK2 activation, and dose-dependently increased the expression of fibronectin, collagen IV and TGF-β1. Pretreatment with curcumin, an inhibitor of JAK2 and p300, blocked Ang II-induced effects. Knockdown of p300 significantly decreased STAT3 acetylation on Lys685, and abolished Ang II-stimulated STAT3 phosphorylation on Tyr705, whereas pretreatment of the cells with C646, a selective inhibitor of p300, inhibited Ang II-induced STAT3 nuclear translocation and the expression of TGF-β1, collagen IV and fibronectin. Pretreatment of the cells with AG490, a JAK2 inhibitor, markedly inhibited Ang II-induced STAT3 phosphorylation on Tyr705 and fibronectin expression. CONCLUSION: p300-dependent STAT3 acetylation is necessary for Ang II-induced STAT3 phosphorylation and the consequent pro-fibrotic responses in renal tubular epithelial cells in vitro. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/25088002/P300_dependent_STAT3_acetylation_is_necessary_for_angiotensin_II_induced_pro_fibrotic_responses_in_renal_tubular_epithelial_cells_ L2 - https://doi.org/10.1038/aps.2014.54 DB - PRIME DP - Unbound Medicine ER -