Bone morphogenetic protein signaling suppresses wound-induced skin repair by inhibiting keratinocyte proliferation and migration.
Bone morphogenetic protein signaling suppresses wound-induced skin repair by inhibiting keratinocyte proliferation and migration.
复制标题
骨形态发生蛋白信号传导通过抑制角质形成细胞增殖和迁移来抑制伤口诱导的皮肤修复。
DOI：
10.1038/jid.2013.419
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发表时间：
2014-03
影响因子：
6.5
通讯作者：
Sharov, Andrey A.
中科院分区：
文献类型：
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作者：
Lewis, Christopher J.;Mardaryev, Andrei N.;Poterlowicz, Krzysztof;Sharova, Tatyana Y.;Aziz, Ahmar;Sharpe, David T.;Botchkareva, Natalia V.;Sharov, Andrey A.
骨形态发生蛋白（BMP）信号通过调节角质形成细胞的增殖、分化和凋亡，在皮肤发育和出生后重塑的控制中起着关键作用。为了研究骨形成蛋白在创伤诱导的表皮修复中的作用，我们使用了在K14启动子控制下过度表达BMP下游组分Smad 1的转基因小鼠作为体内模型，以及离体和体外试验。K14-caSmad 1小鼠表现出延迟的伤口愈合，与愈合伤口上皮细胞的增殖显著抑制和凋亡增加相关。此外，微阵列和qRT-PCR分析显示，与野生型对照相比，K14-caSmad 1小鼠在伤口愈合期间表皮中的许多细胞骨架/细胞运动相关基因（包括伤口相关角蛋白（Krt 16，Krt 17）和Myo 5a）的表达降低。BMP治疗显着抑制角质形成细胞迁移离体，和原代角质形成细胞的K14-caSmad 1小鼠表现出延迟迁移相比，野生型对照。最后，siRNA介导的沉默Bmpr-1B在原代小鼠角质形成细胞加速细胞迁移，并与增加的表达Krt 16，Krt 17和Myo 5a相比，控制。因此，这项研究表明，BMP抑制角质形成细胞增殖，细胞骨架组织和迁移在伤口愈合过程中再生皮肤上皮，并提出了一种可能性，使用BMP拮抗剂的管理慢性伤口。
Bone morphogenetic protein (BMP) signalling plays a key role in the control of skin development and postnatal remodelling by regulating keratinocyte proliferation, differentiation and apoptosis. To study the role of BMPs in wound-induced epidermal repair, we used transgenic mice overexpressing the BMP downstream component Smad1 under the control of a K14 promoter as an in vivo model, as well as ex vivo and in vitro assays. K14-caSmad1 mice exhibited retarded wound healing associated with significant inhibition of proliferation and increased apoptosis in healing wound epithelium. Furthermore, microarray and qRT-PCR analyses revealed decreased expression of a number of cytoskeletal/cell motility-associated genes including wound-associated keratins (Krt16, Krt17) and Myo5a, in the epidermis of K14-caSmad1 mice versus wild-type controls during wound healing. BMP treatment significantly inhibited keratinocyte migration ex vivo, and primary keratinocytes of K14-caSmad1 mice showed retarded migration compared to wild-type controls. Finally, siRNA-mediated silencing of Bmpr-1B in primary mouse keratinocytes accelerated cell migration and was associated with increased expression of Krt16, Krt17 and Myo5a compared to controls. Thus, this study demonstrates that BMPs inhibit keratinocyte proliferation, cytoskeletal organization and migration in regenerating skin epithelium during wound healing, and raises a possibility for using BMP antagonists for the management of chronic wounds.
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影响因子：
2.4
作者：
Hwang, EA;Lee, HB;Tark, KC
通讯作者：
Tark, KC
DOI：
10.1073/pnas.91.12.5528
发表时间：
1994-06-07
影响因子：
11.1
作者：
DROZDOFF, V;WALL, NA;PLEDGER, WJ
通讯作者：
PLEDGER, WJ
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1038/jid.2009.259
发表时间：
2010-02
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
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