p300/p53/Smad3 通路参与人心房成纤维细胞衰老相关心房纤维化

作者:Lai Ying-Yu; Gao Xiao-Yan; Zhou Hui-Shan; Li Xin; Wang Zhao-Yu; Peng De-Wei; Rao Fang*; Deng Chun-Yu*
来源:Chinese Journal of Pathophysiology, 2021, 37(1): 18-26.
DOI:10.3969/j.issn.1000-4718.2021.01.003

摘要

AIM:To investigate the role of p300 in aging-related atrial fibrosis in human atrial fibroblasts (HAFs)and its potential mechanism. METHODS:HAFs were obtained from human left atrial tissue, and the senescence model was established by cell passage. Senescence-associated β-galactosidase(SA-β-Gal)staining was used to detect the cell senescence, and Western blot was used to determine the protein levels of p300, p53, Smad3 and other senescence and fibrosis associated proteins in HAFs. RESULTS:Compared to passage 3 HAFs, the proportion of senescent cells, and the protein levels of p300, p53, p-Smad3 and other senescence and fibrosis associated proteins were increased in HAFs at passage 7 and 11(P<0. 05). After treated with curcumin(a p300 inhibitor)or transfection with p300 small-hairpin(sh)RNA plasmid, the protein levels of p300, and the senescence and fibrosis associated proteins were decreased in HAFs at passage 7(P<0. 05). Up-regulation of p300 by transfection with p300 over-expression plasmid increased the protein levels of p53, Smad3 and MMP-2 in HAFs at passage 3(P<0. 05). CONCLUSION:p300/p53/Smad3 signaling pathway plays an important role in aging-related atrial fibrosis in HAFs. ? 2021 Editorial Board of Chinese Journal of Pathophysiology, Jinan University.

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