Perlecan expression influences the keratin 15-positive cell population fate in the epidermis of aging skin
Perlecan expression influences the keratin 15-positive cell population fate in the epidermis of aging skin
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DOI：
10.18632/aging.100928
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发表时间：
2016-04-01
期刊：
影响因子：
5.2
通讯作者：
Rousselle, Patricia
中科院分区：
文献类型：
--
作者：
Dos Santos, Morgan;Michopoulou, Anna;Rousselle, Patricia
通过干细胞的增殖和分化，表皮不断更新。基底角质形成细胞附着在真皮-表皮交界处，这是一种与细胞表面相关的细胞外基质，提供结构支持并影响它们的行为。它由层粘连蛋白、IV型胶原、尼多芬和Perlecan组成，这些都是组织组织和结构完整性所必需的。Perlecan是一种已知参与角质形成细胞存活和分化的硫酸肝素蛋白多糖。衰老影响真皮表皮交界处，导致与角质形成细胞接触减少，从而影响表皮更新和动态平衡。我们发现，在慢性皮肤老化过程中，Perlecan的表达减少。我们的体外研究显示，在衰老的角质形成细胞中，Perlecan转录水平降低。体外皮肤模型的制作表明，老化的角质形成细胞形成了一层薄而组织不良的表皮。用纯化的Perlecan补充这些模型可以逆转这一现象，允许恢复分化良好的多层上皮。培养的角质形成细胞中Perlecan的下调导致表达角蛋白15的细胞群枯竭。这一现象依赖于Perlecan的硫酸肝素部分，这表明一种生长因子的参与。最后，我们发现角蛋白15在老化皮肤的表皮中表达存在缺陷。这项研究强调了Perlecan在维持基底角质形成细胞自我更新能力方面的新作用。
The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal-epidermal junction, a cell surface-associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well-differentiated multi-layered epithelium. Perlecan down-regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self-renewal capacity of basal keratinocytes.