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  3. Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway

Mechanistic insights into 5-aminolevulinic acid photodynamic therapy for acne vulgaris: targeting lipogenesis via the OLR1-Wnt/β-catenin pathway

  • Mol Med. 2025 Feb 4;31(1):41. doi: 10.1186/s10020-025-01104-w.
Jia Yan # 1,  Linglin Zhang # 1 2,  Qingyu Zeng 1,  Yitao Qian 3,  Ke Li 3,  Xiaojing Liu 1,  Yun Wu 1,  Yu Yan 1,  Haiyan Zhang 1,  Szeman Cheung 3,  Jia Liu 1,  Ronald Sroka 4,  Xiuli Wang 5,  Lei Shi 6
Affiliations

Affiliations

  • 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092,, China.
  • 2 Laser-Forschungslabor, LIFE Center, University Hospital, Ludwig-Maximilian University, 82152, Planegg, Germany.
  • 3 Department of Dermatology, Huadong Hospital, Fudan University, Shanghai, 200040, P. R. China.
  • 4 Laser-Forschungslabor, LIFE Center, University Hospital, Ludwig-Maximilian University, 82152, Planegg, Germany. Ronald.Sroka@med.uni-muenchen.de.
  • 5 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092,, China. wangxiuli_1400023@tongji.edu.cn.
  • 6 Department of Dermatology, Huadong Hospital, Fudan University, Shanghai, 200040, P. R. China. shi_lei@fudan.edu.cn.
  • # Contributed equally.
PMID: 39905294 DOI: 10.1186/s10020-025-01104-w
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.

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