The stress-responsive gene ATF3 drives fibroblast activation and collagen production through transcriptionally activating TGF-β receptor Ⅱ in skin wound healing

  • Arch Biochem Biophys. 2024 Oct:760:110134. doi: 10.1016/j.abb.2024.110134.
Peng Luo  1 ,  Fulong Wang  1 ,  Jialun Li  1 ,  Gaoyu Liu  1 ,  Qin Xiong  1 ,  Benhuang Yan  1 ,  Xiaohui Cao  1 ,  Bao Liu  2 ,  Yang Wang  1 ,  Gang Wu  3 ,  Chunmeng Shi  4
Affiliations
  • 1. Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, 400038, China.
  • 2. Institute of Medicine and Equipment for High Altitude Region, Key Laboratory of Extreme Environmental Medicine of Ministry of Education, Army Medical University, Chongqing, 400038, China.
  • 3. Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, 400038, China; Institute of Medicine and Equipment for High Altitude Region, Key Laboratory of Extreme Environmental Medicine of Ministry of Education, Army Medical University, Chongqing, 400038, China. Electronic address: [email protected].
  • 4. Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, 400038, China. Electronic address: [email protected].
PMID: 39181381 DOI: 10.1016/j.abb.2024.110134
Abstract

Skin wound is an emerging health challenge on account of the high-frequency trauma, surgery and chronic refractory ulcer. Further study on the disease biology will help to develop new effective approaches for wound healing. Here, we identified a wound-stress responsive gene, activating transcription factor 3 (ATF3), and then investigated its biological action and mechanism in wound healing. In the full-thickness skin wound model, ATF3 was found to promote fibroblast activation and Collagen production, resulted in accelerated wound healing. Mechanically, ATF3 transcriptionally activated TGF-β Receptor Ⅱ via directly binding to its specific promoter motif, followed by the enhanced TGF-β/Smad pathway in fibroblasts. Moreover, the increased ATF3 upon skin injury was partly resulted from hypoxia stimulation with HIF-1α dependent manner. Altogether, this work gives novel insights into the biology and mechanism of stress-responsive gene ATF3 in wound healing, and provides a potential therapeutic target for treatment.

Keywords
Activating transcription factor 3; Collagen; Fibroblast; Skin wound healing; TGF-β receptor Ⅱ.
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