Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes.
Protein kinase D1 deficiency promotes differentiation in epidermal keratinocytes.
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DOI：
10.1016/j.jdermsci.2014.09.007
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发表时间：
2014-12
影响因子：
4.6
通讯作者：
Bollag WB
中科院分区：
文献类型：
--
作者：
Choudhary V;Olala LO;Kaddour-Djebbar I;Helwa I;Bollag WB
蛋白激酶D（PKD或PKD 1）是一种丝氨酸/苏氨酸蛋白激酶，已被证明在各种细胞过程中发挥作用;然而，PKD 1在皮肤中的功能尚未得到充分研究。表皮的主要细胞（角质形成细胞）的增殖和分化过程之间的平衡对于正常皮肤功能是必不可少的。研究PKD 1缺陷对表皮角质形成细胞增殖和分化的影响。我们利用了一个floxed PKD 1小鼠模型，使感染表皮角质形成细胞从这些小鼠与腺病毒表达Cre重组酶，使我们能够确定PKD 1基因丢失的影响在体外。使用qRT-PCR、蛋白质印迹、转氨酶活性测定、[3 H]胸苷掺入DNA和细胞周期分析监测增殖和分化。在腺病毒Cre重组酶感染的细胞中，PKD 1 mRNA和蛋白水平显著降低。PKD 1的缺乏导致各种分化标志物如兜甲蛋白、外皮蛋白和角蛋白10的mRNA和蛋白表达显著增加，无论是基底还是分化刺激。PKD 1缺陷的角质形成细胞也表现出转氨酶表达和活性的增加，表明PKD 1的抗分化作用。此外，PKD 1缺陷型角质形成细胞表现出增殖降低。然而，PKD 1丢失对干细胞标志物表达没有影响。Cre重组酶介导的敲低代表了另一种方法，证明PKD 1是小鼠角质形成细胞中的抗分化、促增殖信号。
Protein kinase D (PKD or PKD1) is a serine/threonine protein kinase that has been shown to play a role in a variety of cellular processes; however, the function of PKD1 in the skin has not been fully investigated. The balance between proliferation and differentiation processes in the predominant cells of the epidermis, the keratinocytes, is essential for normal skin function. To investigate the effect of PKD1 deficiency on proliferation and differentiation of epidermal keratinocytes. We utilized a floxed PKD1 mouse model such that infecting epidermal keratinocytes derived from these mice with an adenovirus expressing Cre-recombinase allowed us to determine the effect of PKD1 gene loss in vitro. Proliferation and differentiation were monitored using qRT-PCR, Western blot, transglutaminase activity assays, [3H]thymidine incorporation into DNA and cell cycle analysis. A significant decrease in PKD1 mRNA and protein levels was achieved in adenoviral Cre-recombinase-infected cells. Deficiency of PKD1 resulted in significant increases in the mRNA and protein expression of various differentiation markers such as loricrin, involucrin, and keratin 10 either basally and/or upon stimulation of differentiation. PKD1-deficient keratinocytes also showed an increase in transglutaminase expression and activity, indicating an anti-differentiative role of PKD1. Furthermore, the PKD1-deficient keratinocytes exhibited decreased proliferation. However, PKD1 loss had no effect on stem cell marker expression. Cre-recombinase-mediated knockdown represents an additional approach demonstrating that PKD1 is an anti-differentiative, pro-proliferative signal in mouse keratinocytes.
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影响因子：
8
作者：
Arun, S. N.;Kaddour-Djebbar, I.;Shapiro, B. A.;Bollag, W. B.
通讯作者：
Bollag, W. B.
蛋白激酶 D 信号传导在胰腺癌中的作用。
影响因子：
5.8
作者：
Guha, Sushovan;Tanasanvimon, Suebpong;Sinnett-Smith, James;Rozengurt, Enrique
通讯作者：
Rozengurt, Enrique
影响因子：
3.7
作者：
Chen X;Liu P;Chou HH
通讯作者：
Chou HH
影响因子：
3
作者：
ISHIDAYAMAMOTO, A;HOHL, D;EADY, RAJ
通讯作者：
EADY, RAJ
影响因子：
6.5
作者：
KIM, SY;CHUNG, SI;STEINERT, PM
通讯作者：
STEINERT, PM