Protein kinase D1 has a key role in wound healing and skin carcinogenesis.
Protein kinase D1 has a key role in wound healing and skin carcinogenesis.
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DOI：
10.1038/jid.2013.474
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发表时间：
2014-04
影响因子：
6.5
通讯作者：
Ghazizadeh, Soosan
中科院分区：
文献类型：
--
作者：
Rashel, Mohammad;Alston, Ninche;Ghazizadeh, Soosan
蛋白激酶D（PKD）是一个应激反应性丝氨酸/苏氨酸激酶家族，涉及多种细胞功能的调节，包括细胞生长、分化、凋亡和细胞运动。虽然所有三种亚型都在角质形成细胞中表达，但它们在皮肤生物学和病理学中的作用知之甚少。我们最近确定了一个关键的作用PKD 1在逆转角质形成细胞分化的文化，这表明一个潜在的促增殖作用，表皮适应性反应。在这里，我们产生的小鼠与靶向删除PKD 1的表皮，以评估PKD 1在正常和增生条件下的意义。这些小鼠表现出正常的皮肤表型，表明PKD 1对皮肤发育和体内平衡是有利的。然而，在创伤后，PKD 1缺陷型小鼠表现出延迟的伤口再上皮化，这与伤口边缘角质形成细胞的增殖和迁移减少有关。此外，局部佛波醇酯的增生和炎症反应显着抑制，提示PKD 1参与肿瘤促进。一致的是，当进行两阶段化学皮肤致癌方案时，PKD 1缺陷型小鼠与对照同窝小鼠相比对乳头状瘤形成具有抗性。这些结果揭示了PKD 1在表皮适应性反应中的关键促增殖作用，表明了皮肤创伤和癌症治疗中的潜在治疗靶点。
Protein kinase D (PKD) is a family of stress-responsive serine/threonine kinases implicated in the regulation of diverse cellular functions including cell growth, differentiation, apoptosis, and cell motility. Although all three isoforms are expressed in keratinocytes, their role in skin biology and pathology is poorly understood. We recently identified a critical role for PKD1 during reversal of keratinocyte differentiation in culture, suggesting a potential pro-proliferative role in epidermal adaptive responses. Here, we generated mice with targeted deletion of PKD1 in epidermis to evaluate the significance of PKD1 in normal and hyperplastic conditions. These mice displayed a normal skin phenotype indicating that PKD1 is dispensable for skin development and homeostasis. Upon wounding however, PKD1-deficient mice exhibited delayed wound re-epithelialization correlated with a reduced proliferation and migration of keratinocytes at the wound edge. In addition, the hyperplastic and inflammatory responses to topical phorbol ester were significantly suppressed suggesting involvement of PKD1 in tumor promotion. Consistently, when subjected to two-stage chemical skin carcinogenesis protocol, PKD1-deficient mice were resistant to papilloma formation when compared to control littermates. These results revealed a critical pro-proliferative role for PKD1 in epidermal adaptive responses, suggesting a potential therapeutic target in skin wound and cancer treatment.
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DOI：
10.1152/physiol.00037.2010
发表时间：
2011-02
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Rozengurt E
通讯作者：
Rozengurt E
影响因子：
5.2
作者：
Rundhaug JE;Fischer SM
通讯作者：
Fischer SM
影响因子：
5.3
作者：
Nikolopoulos, SN;Blaikie, P;Giancotti, FG
通讯作者：
Giancotti, FG
影响因子：
11.2
作者：
Hara, T;Saito, Y;Chida, K
通讯作者：
Chida, K
影响因子：
10.3
作者：
Ristich, VL;Bowman, PH;Bollag, WB
通讯作者：
Bollag, WB