2. Academic Validation
  3. YAP1 facilitates the pathogenesis of psoriasis via modulating keratinocyte proliferation and inflammation

YAP1 facilitates the pathogenesis of psoriasis via modulating keratinocyte proliferation and inflammation

  • Cell Death Dis. 2025 Mar 19;16(1):186. doi: 10.1038/s41419-025-07521-3.
Cong Huang # 1 2,  Wenting Li # 3 4,  Changbing Shen # 3 5,  Bin Jiang # 3 5,  Kaoyuan Zhang 3,  Xiahong Li 3,  Weilong Zhong 3,  Zizhuo Li 3,  Zhenzhen Chen 3,  Chaofeng Chen 3,  Xingling Jian 3,  Xiaoming Liu 3,  Haiyan Huang 3,  Lili Yang 3,  Bo Yu 6 7
Affiliations

Affiliations

  • 1 Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. conghuangphd1988@163.com.
  • 2 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. conghuangphd1988@163.com.
  • 3 Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
  • 4 The Digestive and Reproductive System Cancers Precise Prevention Engineering Research Center of Jiangsu Province, Institute of Medicinal Biotechnology, Jiangsu College of Nursing, Huai' an, Jiangsu, China.
  • 5 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
  • 6 Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. drboyu_derm@126.com.
  • 7 Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. drboyu_derm@126.com.
  • # Contributed equally.
PMID: 40108109 DOI: 10.1038/s41419-025-07521-3
Abstract

Psoriasis is an autoinflammatory skin disease characterized by the abnormal activation of epidermal keratinocytes. The Hippo-YAP pathway is an evolutionarily conserved pathway that plays important roles in organ size control and tumorigenesis. Recently, accumulating evidence demonstrated that YAP1, the core downstream component of Hippo-YAP pathway, was up-regulated in psoriasis patients, suggesting its possible role in psoriasis development. However, its precise function and mechanism in psoriasis pathogenesis are still not well-clarified. In the present study, we confirmed the up-regulation of YAP1 in psoriasis keratinocytes by measuring its expression in psoriatic patient skins, psoriatic-like cellular model, and IMQ-induced mouse model. Further functional studies showed that YAP1 promoted keratinocyte proliferation and inflammation in vitro. Meanwhile, VP, a selective YAP1 antagonist, inhibited keratinocyte proliferation and inflammatory factor production in a dose-dependent way. Moreover, intradermal injection of si-Yap1 or VP hindered psoriasis development by impeding epidermal hyperplasia and relieving systemic inflammatory response in the IMQ-induced mouse model. Therefore, our findings suggest that YAP1 plays a crucial role in psoriasis pathogenesis through modulating keratinocyte activation and may serve as a novel target for the treatment of psoriasis.

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