Fibroblasts are the primary regulator of cardiac extracellular matrix (ECM). In response to disease stimuli cardiac fibroblasts undergo cell state transitions to a myofibroblast phenotype, which underlies the fibrotic response in the heart and other organs. Identifying regulators of fibroblast state transitions would inform which pathways could be therapeutically modulated to tactically control maladaptive extracellular matrix remodeling. Indeed, a deeper understanding of fibroblast cell state and plasticity is necessary for controlling its fate for therapeutic benefit. p38 mitogen activated protein kinase (MAPK), which is part of the noncanonical transforming growth factor β (TGFβ) pathway, is a central regulator of fibroblast to myofibroblast cell state transitions that is activated by chemical and mechanical stress signals. Fibroblast intrinsic signaling, local and global cardiac mechanics, and multicellular interactions individually and synergistically impact these state transitions and hence the ECM, which will be reviewed here in the context of cardiac fibrosis.

成纤维细胞是心脏细胞外基质（ECM）的主要调节者。为了响应疾病刺激，心脏成纤维细胞经历细胞状态转变为肌成纤维细胞表型，这是心脏和其他器官纤维化反应的基础。识别成纤维细胞状态转变的调节因子将告知哪些途径可以进行治疗性调节，以策略性地控制适应不良的细胞外基质重塑。事实上，对成纤维细胞状态和可塑性的更深入了解对于控制其命运以获得治疗效果是必要的。 p38 丝裂原激活蛋白激酶 (MAPK) 是非经典转化生长因子 β (TGFβ) 途径的一部分，是由化学和机械应激信号激活的成纤维细胞向肌成纤维细胞状态转变的中央调节因子。成纤维细胞内在信号传导、局部和整体心脏力学以及多细胞相互作用单独和协同地影响这些状态转换，从而影响 ECM，本文将在心脏纤维化的背景下对其进行综述。