An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
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DOI：
10.1016/j.devcel.2014.11.012
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发表时间：
2014-12-22
影响因子：
11.8
通讯作者：
Campisi, Judith
中科院分区：
文献类型：
--
作者：
Demaria, Marco;Ohtani, Naoko;Youssef, Sameh A.;Rodier, Francis;Toussaint, Wendy;Mitchell, James R.;Laberge, Remi-Martin;Vijg, Jan;Van Steeg, Harry;Dolle, Martijn E. T.;Hoeijmakers, Jan H. J.;de Bruin, Alain;Hara, Eiji;Campisi, Judith
细胞衰老通过阻止癌前细胞的生长来抑制癌症，然而衰老细胞的积累被认为通过衰老相关分泌表型（SASP）驱动年龄相关的病理学，其功能尚不清楚。为了理解复杂衰老表型的生理作用，我们产生了一种小鼠模型，其中衰老细胞可以在活体动物中可视化和消除。我们发现，衰老的成纤维细胞和内皮细胞出现非常早的皮肤伤口，在那里他们通过诱导肌成纤维细胞分化，通过分泌血小板衍生生长因子AA（PDGF-AA）加速伤口愈合。在两种小鼠模型中，用重组PDGF-AA局部治疗无衰老伤口挽救了延迟的伤口闭合和肌成纤维细胞分化的缺乏。这些发现定义了SASP在组织修复中的有益作用，并有助于解释SASP进化的原因。
Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.
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影响因子：
3.7
作者：
Coppé JP;Patil CK;Rodier F;Krtolica A;Beauséjour CM;Parrinello S;Hodgson JG;Chin K;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
3.3
作者：
Freund A;Laberge RM;Demaria M;Campisi J
通讯作者：
Campisi J
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
64.5
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
通讯作者：
Sharpless NE
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J