Title: Intercellular contact is sufficient to drive Fibroblast to Myofibroblast transitions Show Chinese title

Title: 细胞间接触足以驱动成纤维细胞向肌成纤维细胞的转变

Abstract: Fibroblast cells play a key role in maintaining the extracellular matrix. During wound healing, fibroblasts differentiate into highly contractile myofibroblasts, which secrete extracellular matrix proteins like collagen to facilitate tissue repair. Under normal conditions, myofibroblasts undergo programmed cell death after healing to prevent excessive scar formation. However, in diseases like fibrosis, the myofibroblasts remain active even after the wound is closed, resulting in excessive collagen buildup and a stiff, fibrotic matrix. The reasons for the persistence of myofibroblasts in fibrosis are not well understood. Here we show the existence of a mechanism where direct physical contact between a fibroblast and a myofibroblast is sufficient for fibroblasts to transition into myofibroblasts. We show that fibroblast-myofibroblast transition can occur even in the absence of known biochemical cues such as growth factor activation or mechanical cues from a stiff, fibrotic matrix. Further, we show that contact-based fibroblast-myofibroblast activation can be blocked by G{\alpha}q/11/14 inhibitor FR9003591, which inhibits the formation of myofibroblasts. These findings offer new insights into the persistence of fibrosis despite therapeutic interventions and suggest a potential strategy to target fibroblast-to-myofibroblast transition in fibrosis. Show Chinese abstract

Abstract: 成纤维细胞在维持细胞外基质中起关键作用。 在伤口愈合过程中，成纤维细胞分化为高度收缩的肌成纤维细胞，分泌胶原等细胞外基质蛋白以促进组织修复。 在正常情况下，肌成纤维细胞在愈合后会发生程序性细胞死亡，以防止过度的瘢痕形成。 然而，在如纤维化等疾病中，即使伤口已闭合，肌成纤维细胞仍保持活跃，导致胶原过度积累和僵硬的纤维化基质。 纤维化中肌成纤维细胞持续存在的原因尚不明确。 在这里，我们展示了存在一种机制，即成纤维细胞与肌成纤维细胞之间的直接物理接触足以使成纤维细胞转变为肌成纤维细胞。 我们证明，即使在缺乏已知的生化信号（如生长因子激活或来自僵硬纤维化基质的机械信号）的情况下，成纤维细胞-肌成纤维细胞转化仍可能发生。 此外，我们表明，基于接触的成纤维细胞-肌成纤维细胞激活可被G{\alpha }q/11/14抑制剂FR9003591阻断，该抑制剂抑制肌成纤维细胞的形成。 这些发现为尽管有治疗干预纤维化仍然持续提供了新的见解，并暗示了一种针对纤维化中成纤维细胞向肌成纤维细胞转化的潜在策略。