Impact of phosphate toxicity on skin aging

磷酸盐毒性对皮肤老化的影响

• 批准号: 24659527
• 负责人: OGAWA Yasushi
• 金额: $ 2.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659527/
• 关键词: ケラチノサイト; 老化; リン代謝; 皮膚病態学; 代謝調節

Hyperphosphatemia is caused by several diseases including chronic renal failure, and is often accompanied by skin manifestations that mimic aging. The "phosphate toxicity" hypothesis suggests that hyperphosphatemia induce aging like symptoms of the body, however, the direct consequence of the high phosphate condition on keratinocytes was not well studied.In this study we verified that normal human epidermal keratinocytes (NHEK) are driven into early cellular senescence if cultured under non-optimum phosphate condition. NHEK showed highest population doubling levels (PDL) when cultured in 4 mM phosphate and the concentration lower or higher than this level resulted in decreased PDL. The decrease in PDL was accompanied by increased expression of keratinocyte differentiation markers. No increase in senescence associated secreted proteins was observed. It may be suggested that high phosphate condition may drive NHEK to differentiated state leading to accelerated aging-like phenotype.

高磷酸盐血症是由包括慢性肾衰竭在内的多种疾病引起的，并且通常伴有模拟衰老的皮肤表现。“磷酸盐毒性”假说认为高磷酸盐血症可导致机体出现衰老样症状，然而，高磷酸盐条件对角质形成细胞的直接影响还没有得到很好的研究，在本研究中，我们证实了正常人表皮角质形成细胞（NHEK）在非最佳磷酸盐条件下培养会被驱动进入早期细胞衰老。当在4mM磷酸盐中培养时，NHEK显示出最高的群体倍增水平（PDL），并且低于或高于该水平的浓度导致PDL降低。PDL的减少伴随着角质形成细胞分化标志物表达的增加。未观察到衰老相关分泌蛋白的增加。提示高磷条件可促使NHEK向分化状态发展，导致加速衰老样表型。

项目成果

慢性腎不全患者における老化様皮膚の形成機構の解明

阐明慢性肾功能衰竭患者皮肤老化的形成机制

• 发表时间: 2012
• 作者: Mika Terao;Hiroyuki Murota;Ichiro Katayama;小川靖
• 通讯作者: 小川靖

慢性腎不全者患者における老化様皮膚の形成機構の解明

阐明慢性肾功能衰竭患者皮肤老化的形成机制

• 发表时间: 2012
• 作者: Mika Terao;Hiroyuki Murota;Ichiro Katayama;小川靖;小川靖
• 通讯作者: 小川靖