The role of Sprouty1 in the proliferation, differentiation and apoptosis of epidermal keratinocytes.
The role of Sprouty1 in the proliferation, differentiation and apoptosis of epidermal keratinocytes.
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Sprouty1在表皮角质形成细胞增殖、分化和凋亡中的作用。
DOI：
10.1111/cpr.12477
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发表时间：
2018
影响因子：
8.5
通讯作者：
Man Xiao-Yong
中科院分区：
文献类型：
--
作者：
Wang Ping;Zhou Yuan;Yang Jian-Qiang;L;eck Lilla;Min Min;Chen Xi-Bei;Chen Jia-Qi;Li Wei;Cai Sui-Qing;Zheng Min;Man Xiao-Yong
SPRY (SPRY) 1是SPRY蛋白中的一种，可抑制多种生长因子信号通路，在多种恶性肿瘤中也被认为是肿瘤抑制因子。然而，没有研究阐明SPRY1在皮肤中的作用。我们的研究是为了确定SPRY1在人角质形成细胞和表皮中的功能。材料与方法采用体外原代培养表皮角质形成细胞，研究表皮角质形成细胞的增殖、分化和凋亡情况。我们还在体外和K14‐SPRY1转基因小鼠中建立了SPRY1的过表达。结果spry1主要存在于表皮角质形成细胞的细胞质中，分布于皮肤颗粒表皮层和培养细胞中。SPRY1在角质形成细胞中过表达导致P21、P27上调，cyclin B1下调；MMP3和整合素α6降低。SPRY1‐过表达的原代角质形成细胞表现出较低的增殖和迁移能力以及较高的凋亡率。SPRY1‐TG小鼠的表皮表现为伤口愈合延迟。蛋白质组学分析和氧化石墨烯富集表明，SPRY1 TG小鼠表皮的DEPs在免疫和炎症相关的生物过程中显著富集。综上所述，SPRY1的表达与角质形成细胞的增殖、迁移及促进细胞凋亡呈负相关。SPRY1可能是正常人表皮角质形成细胞和皮肤炎症反应的负反馈调节因子。我们的研究提出了一种可能性，即增强SPRY1的表达可能具有促进抗炎作用的潜力。
ObjectivesSprouty (SPRY) 1 is one of the SPRY proteins that inhibits signalling from various growth factors pathways and has also been known as a tumour suppressor in various malignancies. However, no study elucidates the role of SPRY1 in the skin. Our study was conducted to determine the function of SPRY1 in human keratinocytes and the epidermis.Materials and methodsIn vitro primary cultured epidermal keratinocytes were used to investigate the proliferation, differentiation and apoptosis of these cells. We also established overexpression of SPRY1 in vitro and K14‐SPRY1 transgenic mice.ResultsSPRY1 was mainly located in the cytoplasm of the epidermal keratinocytes from the granular epidermal layer of the skin and cultured cells. Overexpressed SPRY1 in keratinocytes resulted in up‐regulation of P21, P27 and down‐regulation of cyclin B1; decrease in MMP3 and integrin α6. SPRY1‐overexpressed primary keratinocytes exhibited a lower proliferation and migration capability and higher rates of apoptosis. Epidermis of SPRY1‐TG mice represented delayed wound healing. Proteomics analysis and GO enrichment showed DEPs of SPRY1 TG mice epidermis is significantly enriched in immune‐ and inflammatory‐associated biological process.ConclusionsIn summary, SPRY1 expression was inversely correlated with cell proliferation, migration and promote cell apoptosis of keratinocytes. SPRY1 maybe a negative feedback regulator in normal human epidermal keratinocytes and cutaneous inflammatory responses. Our study raised the possibility that enhancing expression of SPRY1 may have the potential to promote anti‐inflammatory effects.