Deranged epidermal differentiation in kl/kl mouse and the effects of βKlotho siRNA on the differentiation of HaCaT cells

Deranged epidermal differentiation in kl/kl mouse and the effects of βKlotho siRNA on the differentiation of HaCaT cells
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kl/kl小鼠表皮分化紊乱及βKlotho siRNA对HaCaT细胞分化的影响

DOI:
10.1111/exd.12258
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发表时间:
2013
影响因子:
3.6
通讯作者:
S. Inoue
S. Inoue
中科院分区:
医学2区
文献类型:
--
作者:
K. Nakai;K. Yoneda;R. Haba;Y. Kushida;N. Katsuki;T. Moriue;H. Kosaka;Y. Kubota;S. Inoue

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缺乏klotho基因的小鼠(kl/kl小鼠)显示出人类衰老的表型。我们发现,表皮分化相关因子(角蛋白1、角蛋白10、聚丝蛋白和兜甲蛋白)在kl/kl小鼠皮肤中的表达低于野生型小鼠。体外实验表明,当在空气-液体界面中培养永生化人表皮角质形成细胞系(HaCaT细胞)时,βKlotho(klotho基因编码蛋白家族)的表达伴随着其分化而被诱导。通过小干扰核糖核酸敲低βKlotho抑制HaCaT细胞中上述分化相关因子的表达。βKlotho小干扰核糖核酸增加了角蛋白14的表达,角蛋白14在有丝分裂活性的基底层细胞中表达,并激活了在气液界面中生长的HaCaT细胞中的p44/p42有丝分裂原活化蛋白激酶。提示kl/kl小鼠表皮分化紊乱,βKlotho是人表皮角质形成细胞分化所必需的。
Mice deficient in the klotho gene (kl/kl mice) display the phenotypes of human ageing. We found that the expression of epidermal differentiation‐associated factors (keratin 1, keratin 10, filaggrin and loricrin) was lower in the skin of kl/kl mice than that of wild‐type mice. In vitro experiments showed that the expression of βKlotho, a family of klotho gene‐encoded protein, was induced concomitantly with the differentiation of an immortalized human epidermal keratinocyte cell line (HaCaT cells) when they were cultured in an air–liquid interface. βKlotho knockdown by small interfering ribonucleic acid suppressed the expression of the above differentiation‐associated factors in HaCaT cells. βKlotho small interfering ribonucleic acid increased the expression of keratin 14, which is expressed in mitotically active basal layer cells, and activated p44/p42 mitogen‐activated protein kinase in the HaCaT cells grown in the air–liquid interface. These findings suggest that the epidermal differentiation is deranged in kl/kl mice, and βKlotho is required for the differentiation of human epidermal keratinocytes.
DOI: 10.1126/science.1112766
发表时间: 2005-09-16
期刊: SCIENCE
影响因子: 56.9
作者:
Kurosu, H;Yamamoto, M;Kuro-o, M
通讯作者: Kuro-o, M
DOI: 10.1016/s0167-4781(02)00281-6
发表时间: 2002-07-19
期刊: BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子: --
作者:
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通讯作者: Nabeshima, Y
DOI: 10.1038/36285
发表时间: 1997-11-06
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Nabeshima, Y