转录辅激活因子和乙酰基转移酶p300在心脏 成纤维细胞衰老相关纤维化中的作用

作者:Gao Xiao-Yan; Li Xin; Wei Jian-Qin; Nanette Hahr Bishopric; Wang Zhao-Yu; Zhou Hui-Shan; Rao Fang*; Deng Chun-Yu*
来源:Chinese Journal of Pathophysiology, 2019, 35(12): 2113-2120.
DOI:10.3969/j.issn.1000-4718.2019.12.001

摘要

AIM: To investigate the role of co-transcriptional activator and acetyltransferase p300 in aging-related fibrosis of cardiac fibroblasts ( CFs). METHODS: The protein expression of p300, collagen type I α1 chain (Col1A1), matrix metalloproteinase-2 (MMP-2), transforming growth factor-β (TGF-β), tumor suppressor protein p53 and cyclin-dependent kinase inhibitor p21 in C57BL/6 mouse left atrium and CFs was assessed by Western blot. Cre enzyme was transfected into primarily cultured CFs of p300+/+ and p300flox/+ mice. The genotype of the cells was determined by PCR. The stably transfected cell lines were selected and established. The gene-silencing efficiency was evaluated by Western blot. Senescence-associated (β-galactosidase (SA-β-Gal) staining and cell counting were used to observe the senescence and proliferation of CFs, respectively. RESULTS: With the increase in age, the protein expression levels of p300, Col1A1, MMP-2, TGF-β, p53 and p21 in mouse left atrium was significantly increased ( P < 0. 05 ). SA-β-Gal staining showed that the percentage of aging cells was higher in passage 18 CFs than that in passage 12 CFs. The protein expression levels of p300, Col1A1, MMP-2, TGF-β, p53 and p21 was significantly increased in passage 11 CFs than that in passage 3 CFs (P <0. 05). The CFs was transfected with Cre enzyme successfully. The SA-p-Gal staining positive cells was decreased and the cell proliferation ability was increased after transfection as compared with control group ( P < 0.05 ). CONCLUSION: In atrial tissue, p300 might be involved in CFs aging and aging-related cardiac fibrosis. ? 2019 Authors.

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