Fibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis. Moreover, inducible p21 silencing during fibrosis development alleviates disease pathology, decreasing the inflammatory response and ECM accumulation in the lung, and reducing the amount of senescent cells. Furthermore, p21 silencing limits fibrosis progression even when introduced during disease development. These findings show that one common mechanism regulates both cell cycle progression and expression of ECM components, and suggest that targeting p21 might be a new approach for treating age-related fibrotic pathologies.

中文翻译：

---

p21 调节 ECM 成分的表达，并通过 CDK4 和 Rb 促进肺纤维化。


衰老细胞的纤维化和积累是与衰老相关的常见组织变化。在这里，我们表明 CDK 抑制剂 p21 （CDKN1A） 已知可调节细胞周期和衰老细胞的活力，也以依赖于 CDK4 和 Rb 磷酸化的方式控制纤维化肺衰老和增殖细胞中细胞外基质 （ECM） 成分的表达。p21 敲除可保护小鼠免受肺纤维化的诱导。此外，纤维化发展过程中可诱导的 p21 沉默可缓解疾病病理，减少肺部的炎症反应和 ECM 积累，并减少衰老细胞的数量。此外，即使在疾病发展期间引入 p21 沉默也会限制纤维化进展。这些发现表明，一种共同的机制调节细胞周期进程和 ECM 成分的表达，并表明靶向 p21 可能是治疗与年龄相关的纤维化病变的新方法。