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
  • 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. [email protected].
  • 5. Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092,, China. [email protected].
  • 6. Department of Dermatology, Huadong Hospital, Fudan University, Shanghai, 200040, P. R. China. [email protected].
  • # 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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