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GPCR在皮肤表皮干细胞的景观：巨大的临床潜力

张枝林¹, 马小庆¹, 张肇恬¹, 张荣昊¹, 崔儒涛^2,*

¹浙江大学医学院附属第二医院，杭州 310058；²浙江大学医学院附属第二医院皮肤病研究所，杭州 310058

摘要

皮肤是人体最大的器官，作为抵御感染和损伤的主要屏障，其健康依赖于表皮干细胞的调控，这对于维持表皮稳态、毛发再生和损伤修复至关重要。近年来研究发现，G蛋白耦联受体(G protein-coupled receptor, GPCR)在表皮干细胞命运决定中发挥重要作用。GPCRs的激活会分裂产生Gαs、Gαi 和Gαq，进而调控多种下游信号通路，如WNT-BMP信号交互作用和Gαs-PKA 信号通路，共同影响表皮干细胞的增殖和分化。基于此，GPCR靶向疗法成为改善皮肤健康的新策略，通过精准调控表皮干细胞命运，有望推动皮肤再生与疾病治疗的研究和应用。

关键词： G蛋白耦联受体; 皮肤; 表皮干细胞

The landscape of GPCR in the skin epidermal stem cells: From the basic to the clinical

ZHANG Zhi-Lin¹, MA Xiao-Qing¹, ZHANG Zhao-Tian¹, ZHANG Rong-Hao¹, CUI Ru-Tao^2,*

¹The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310058, China；²Skin Disease Research Institute, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310058, China

Abstract

Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance of skin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, and the repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the context of understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers the subsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstream signaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectively influence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improving skin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.

Key words: G protein-coupled receptor; skin; epidermal stem cells Review This

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通讯作者：崔儒涛　　E-mail:

引用本文：

张枝林, 马小庆, 张肇恬, 张荣昊, 崔儒涛. GPCR在皮肤表皮干细胞的景观：巨大的临床潜力[J]. 生理学报 2024; 76 (6): 881-892.

ZHANG Zhi-Lin, MA Xiao-Qing, ZHANG Zhao-Tian, ZHANG Rong-Hao, CUI Ru-Tao. The landscape of GPCR in the skin epidermal stem cells: From the basic to the clinical. Acta Physiol Sin 2024; 76 (6): 881-892