Pharmacological YAP activation promotes regenerative repair of cutaneous wounds.
Pharmacological YAP activation promotes regenerative repair of cutaneous wounds.
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药理学YAP激活促进皮肤伤口的再生修复。
DOI：
10.1073/pnas.2305085120
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发表时间：
2023-07-11
影响因子：
11.1
通讯作者：
Bollong, Michael J.
中科院分区：
文献类型：
--
作者：
Grzelak, Edyta M.;Elshan, N. G. R. Dayan;Shao, Sida;Bulos, Maya L.;Joseph, Sean B.;Chatterjee, Arnab K.;Chen, Jian Jeffrey;Nguyen-Tran, Van;Schultz, Peter G.;Bollong, Michael J.
数以百万计的美国人患有慢性伤口，包括糖尿病足溃疡、静脉性腿部溃疡和压力性溃疡。尽管这种持续和不断增长的医疗需求，积极加速伤口闭合的治疗方法是有限的。在这里，我们证明，药理学激活的转录辅激活因子雅普，器官大小和细胞增殖的关键调节动物，加速伤口愈合的人类和猪模型的伤口闭合。这项工作可以作为一种新的治疗模式在治疗慢性伤口的基础。慢性皮肤伤口仍然是一个持续未满足的医疗需求，降低了预期寿命和生活质量。在这里，我们报告说，局部应用PY-60，转录辅激活因子是相关蛋白（雅普）的小分子激活剂，促进皮肤伤口的再生修复在猪和人类模型。药理学雅普激活在角质形成细胞和真皮细胞中产生可逆的促增殖转录程序，导致伤口床的加速再上皮化和再肉芽化。这些结果表明，短暂局部施用雅普活化剂可代表治疗皮肤伤口的可推广的治疗方法。
Millions of Americans suffer from chronic wounds, including diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Despite this persistent and growing medical need, therapeutics that actively accelerate wound closure are limited. Here, we demonstrate that pharmacological activation of the transcriptional coactivator YAP, a key regulator of organ size and cellular proliferation in animals, accelerates wound closure in human and pig models of wound healing. This work may serve as the basis for a novel therapeutic paradigm in treating chronic wounds. Chronic cutaneous wounds remain a persistent unmet medical need that decreases life expectancy and quality of life. Here, we report that topical application of PY-60, a small-molecule activator of the transcriptional coactivator Yes-associated protein (YAP), promotes regenerative repair of cutaneous wounds in pig and human models. Pharmacological YAP activation enacts a reversible pro-proliferative transcriptional program in keratinocytes and dermal cells that results in accelerated re-epithelization and regranulation of the wound bed. These results demonstrate that transient topical administration of a YAP activating agent may represent a generalizable therapeutic approach to treating cutaneous wounds.
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影响因子：
23.9
作者：
Mascharak S;Talbott HE;Januszyk M;Griffin M;Chen K;Davitt MF;Demeter J;Henn D;Bonham CA;Foster DS;Mooney N;Cheng R;Jackson PK;Wan DC;Gurtner GC;Longaker MT
通讯作者：
Longaker MT
影响因子：
3.2
作者：
Mallampati, Ramya;Patlolla, Ram R.;Singh, Mandip S.
通讯作者：
Singh, Mandip S.
影响因子：
5.6
作者：
Magadum A;Engel FB
通讯作者：
Engel FB
影响因子：
3
作者：
Knight, EV;Oldham, JW;Dooley, J
通讯作者：
Dooley, J
YAP1在α-catenin的下游作用以控制表皮增殖。
影响因子：
64.5
作者：
Schlegelmilch K;Mohseni M;Kirak O;Pruszak J;Rodriguez JR;Zhou D;Kreger BT;Vasioukhin V;Avruch J;Brummelkamp TR;Camargo FD
通讯作者：
Camargo FD