心脏纤维化是多种心脏疾病中常见的病理性心脏重塑，其特征是心脏成纤维细胞的激活。我们以前的研究发现，前髓样白血病蛋白（PML）相关的SUMO过程是心肌肥大和心力衰竭的一个新调节因子。本研究旨在探讨PML在心脏成纤维细胞的激活中的作用。我们发现，在转化生长因子-β1（TGF-β1）处理过的纤维化心脏组织和活化的心脏成纤维细胞中，PML显著上调。增强和减弱功能实验表明，在TGF-β1处理后，PML影响心脏成纤维细胞的激活。进一步的研究表明，p53作为PML的转录调节因子，并参与了TGF-β1诱导的PML表达增加和PML核小体（PML-NBs）形成。p53的基因沉默或药物抑制对心脏成纤维细胞的激活产生了抑制作用。我们进一步发现，在心脏成纤维细胞中，PML也可以通过抑制其泛素介导的蛋白酶体降解来稳定p53。总之，本研究表明，PML 与 p53的交叉对话调节心脏成纤维细胞的激活，为治疗心脏纤维化提供了一种新的策略。©作者。

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-β1 (TGF-β1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-β1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-β1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.© The author(s).