Journal Article Ppublish 2 citations
PubMed: 40023001 DOI: 10.1016/j.tranon.2025.102331
SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis.
Transl Oncol 54:102331
Authors: Rongxin Zhao, Xun Zhang, Yingnan Geng, Dan Lu, Yuqing Wang, Han Xie, Xiaofei Zhang, Shunming Xu, Yanyun Cao
Affiliations
- Department of Dermatology, Pudong New Area People's Hospital, 490 Chuanhuang South Road, Pudong New Area, Shanghai, China.
- Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
- Department of Burns and Plastic Surgery, Second Affiliated Hospital of Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, China.
- Department of Dermatology, Xuzhou Huamei Cosmetology Hospital, Jiangsu, West Huaihai Road, Quanshan District, Xuzhou, Jiangsu, China.
- The Fifth People's Hospital of Shanghai, Fudan University, No. 128, Ruili Road, Minhang District, Shanghai, China.
- Shanghai Xinmei Medical Beauty Outpatient Department, 202A, No.285, Jianguo West Road, Xuhui District, Shanghai, China.
- Department of Dermatology, Pudong New Area People's Hospital, 490 Chuanhuang South Road, Pudong New Area, Shanghai, China.
- Department of Dermatology, Pudong New Area People's Hospital, 490 Chuanhuang South Road, Pudong New Area, Shanghai, China.
Abstract
INTRODUCTION
Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma.
METHODS
Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.
RESULTS
SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes.
CONCLUSIONS
SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.
MeSH
Skin, Cells, Genes, Melanoma, Aging, Macrophages, Skin Aging, Therapeutics, Prognosis