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  3. Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts

Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts

  • Int J Biol Macromol. 2024 Aug 3;277(Pt 3):134482. doi: 10.1016/j.ijbiomac.2024.134482.
Ying Zou 1,  Mibu Cao 2,  Li Tao 3,  Shu Wu 3,  Haoxian Zhou 4,  Youliang Zhang 2,  Yiqing Chen 2,  Yuanlong Ge 5,  Zhenyu Ju 6,  Shengkang Luo 7
Affiliations

Affiliations

  • 1 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Biology, School of Medicine, Jinan University, Guangzhou, China; Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 2 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Biology, School of Medicine, Jinan University, Guangzhou, China.
  • 3 Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 4 Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 5 Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: geyuanlong@jnu.edu.cn.
  • 6 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Biology, School of Medicine, Jinan University, Guangzhou, China; Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: zhenyuju2016@jnu.edu.cn.
  • 7 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Biology, School of Medicine, Jinan University, Guangzhou, China; Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: luoshk@gd2h.org.cn.
PMID: 39102921 DOI: 10.1016/j.ijbiomac.2024.134482
Abstract

Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.

Keywords

Fibroblasts; Lactylation; PLLA.

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