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The role of Sprouty1 in the proliferation,differentiation and apoptosis of epidermal keratinocytes
Authors:Ping Wang  Yuan Zhou  Jian‐Qiang Yang  Lilla Landeck  Min Min  Xi‐Bei Chen  Jia‐Qi Chen  Wei Li  Sui‐Qing Cai  Min Zheng  Xiao‐Yong Man
Institution:1. Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;2. Ernst von Bergmann General Hospital, Teaching Hospital of the Charité‐University Medicine Berlin, Humboldt University, Potsdam, Germany
Abstract:

Objectives

Sprouty (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 methods

In 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.

Results

SPRY1 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.

Conclusions

In 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.
Keywords:
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