Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway
Abstract Acne vulgaris, a prevalent chronic inflammatory skin disorder, is often characterized by hyperactive sebaceous glands and excessive sebum production, presenting a significant therapeutic challenge. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is clinically effective in treatin...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Molecular Medicine |
| Online Access: | https://doi.org/10.1186/s10020-025-01104-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861973803073536 |
|---|---|
| author | Jia Yan Linglin Zhang Qingyu Zeng Yitao Qian Ke Li Xiaojing Liu Yun Wu Yu Yan Haiyan Zhang Szeman Cheung Jia Liu Ronald Sroka Xiuli Wang Lei Shi |
| author_facet | Jia Yan Linglin Zhang Qingyu Zeng Yitao Qian Ke Li Xiaojing Liu Yun Wu Yu Yan Haiyan Zhang Szeman Cheung Jia Liu Ronald Sroka Xiuli Wang Lei Shi |
| author_sort | Jia Yan |
| collection | DOAJ |
| description | Abstract Acne vulgaris, a prevalent chronic inflammatory skin disorder, is often characterized by hyperactive sebaceous glands and excessive sebum production, presenting a significant therapeutic challenge. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is clinically effective in treating moderate to severe acne, the molecular mechanisms underlying its therapeutic effects remain largely unexplored. In this study, we investigated the impact of ALA-PDT on lipid metabolism in an acne-like mouse model and in immortalized human sebocytes (XL-i-20), focusing on the role of the OLR1-Wnt/β-catenin pathway. We employed transcriptomic analysis, lipid staining, and gene silencing techniques to dissect the molecular interactions induced by ALA-PDT. Our findings revealed that ALA-PDT significantly reduces lipogenesis by upregulating OLR1, which in turn suppresses the SREBP1-FAS axis, thereby decreasing lipid accumulation in sebocytes. Furthermore, activation of the OLR1-Wnt/β-catenin pathway was essential for these lipogenic effects, as silencing OLR1 or activating Wnt/β-catenin signaling reversed lipogenesis inhibition. This study elucidates a novel mechanistic pathway in ALA-PDT-mediated acne treatment, highlighting OLR1 as a promising target for future therapeutic strategies. |
| format | Article |
| id | doaj-art-7c29e2c504554c32a39e93b4f4593dd3 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-7c29e2c504554c32a39e93b4f4593dd32025-02-09T12:42:17ZengBMCMolecular Medicine1528-36582025-02-0131111410.1186/s10020-025-01104-wMechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathwayJia Yan0Linglin Zhang1Qingyu Zeng2Yitao Qian3Ke Li4Xiaojing Liu5Yun Wu6Yu Yan7Haiyan Zhang8Szeman Cheung9Jia Liu10Ronald Sroka11Xiuli Wang12Lei Shi13Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityDepartment of Dermatology, Huadong Hospital, Fudan UniversityDepartment of Dermatology, Huadong Hospital, Fudan UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityDepartment of Dermatology, Huadong Hospital, Fudan UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityLaser-Forschungslabor, LIFE Center, University Hospital, Ludwig-Maximilian UniversityInstitute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji UniversityDepartment of Dermatology, Huadong Hospital, Fudan UniversityAbstract Acne vulgaris, a prevalent chronic inflammatory skin disorder, is often characterized by hyperactive sebaceous glands and excessive sebum production, presenting a significant therapeutic challenge. While 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is clinically effective in treating moderate to severe acne, the molecular mechanisms underlying its therapeutic effects remain largely unexplored. In this study, we investigated the impact of ALA-PDT on lipid metabolism in an acne-like mouse model and in immortalized human sebocytes (XL-i-20), focusing on the role of the OLR1-Wnt/β-catenin pathway. We employed transcriptomic analysis, lipid staining, and gene silencing techniques to dissect the molecular interactions induced by ALA-PDT. Our findings revealed that ALA-PDT significantly reduces lipogenesis by upregulating OLR1, which in turn suppresses the SREBP1-FAS axis, thereby decreasing lipid accumulation in sebocytes. Furthermore, activation of the OLR1-Wnt/β-catenin pathway was essential for these lipogenic effects, as silencing OLR1 or activating Wnt/β-catenin signaling reversed lipogenesis inhibition. This study elucidates a novel mechanistic pathway in ALA-PDT-mediated acne treatment, highlighting OLR1 as a promising target for future therapeutic strategies.https://doi.org/10.1186/s10020-025-01104-w |
| spellingShingle | Jia Yan Linglin Zhang Qingyu Zeng Yitao Qian Ke Li Xiaojing Liu Yun Wu Yu Yan Haiyan Zhang Szeman Cheung Jia Liu Ronald Sroka Xiuli Wang Lei Shi Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway Molecular Medicine |
| title | Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway |
| title_full | Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway |
| title_fullStr | Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway |
| title_full_unstemmed | Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway |
| title_short | Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway |
| title_sort | mechanistic insights into 5 aminolevulinic acid photodynamic therapy for acne vulgaris targeting lipogenesis via the olr1 wnt β catenin pathway |
| url | https://doi.org/10.1186/s10020-025-01104-w |
| work_keys_str_mv | AT jiayan mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT linglinzhang mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT qingyuzeng mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT yitaoqian mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT keli mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT xiaojingliu mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT yunwu mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT yuyan mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT haiyanzhang mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT szemancheung mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT jialiu mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT ronaldsroka mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT xiuliwang mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway AT leishi mechanisticinsightsinto5aminolevulinicacidphotodynamictherapyforacnevulgaristargetinglipogenesisviatheolr1wntbcateninpathway |