以前的研究认为，细胞衰老是一种肿瘤抑制机制，但除了癌症之外，很少有研究探索细胞衰老在其他疾病中的作用。现在，研究人员提出，受蛋白质CCN1调控的细胞衰老可预防受伤期间过多组织的形成，即组织纤维变性。

细胞衰老是指细胞保持存态但失去再分化能力的状态。肉芽组织是伤口愈合期间所形成的一种软组织联接。Jun和Lau发现，衰老的细胞出现在小鼠的肉芽组织中。缺失CCN1功能的小鼠只出现了更少的衰老细胞。他们因此得出结论认为，CCN1调控了细胞的衰老机制，并通过CCN1功能的插入来鉴别这种机制。

他们还发现，缺失CCN1的小鼠，在其伤口愈合期间会出现更多的组织纤维变性。相反，将CCN1插入受伤的组织会导致细胞衰老，从而预防纤维化组织的出现。组织纤维化与多种疾病有关，新数据支持了细胞衰老在抗纤维化机制中的重要作用。

原文出处：

Nature Cell Biology   doi:10.1038/ncb2070

The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing
Joon-Il Jun1 & Lester F. Lau1

Cellular senescence is a recognized mechanism of tumour suppression; however, its contribution to other pathologies is not well understood. We show that the matricellular protein CCN1 (also known as CYR61; cysteine-rich protein 61), which is dynamically expressed at sites of wound repair, can induce fibroblast senescence by binding to integrin α6β1 and the heparan sulphate proteoglycans (receptors involved in cell adhesion). CCN1 induces DNA damage response pathways and activates p53 and the RAC1–NOX1 complex, which generates reactive oxygen species (ROS). This results in the ROS-dependent activation of the p16INK4a/pRb pathway, leading to senescence and concomitant expression of antifibrotic genes. Senescent fibroblasts accumulate in granulation tissues of healing cutaneous wounds and express antifibrotic genes in wild-type mice. These processes are lost in knockin mice that express a senescence-defective Ccn1 mutant, resulting in exacerbated fibrosis. Topical application of CCN1 protein to wounds reverses these defects. Thus, fibroblast senescence is a CCN1-dependent wound healing response in cutaneous injury that functions to curb fibrosis during tissue repair.