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The stress-responsive gene ATF3 drives fibroblast activation and collagen production through transcriptionally activating TGF-β receptor Ⅱ in skin wound healing.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Oct; Vol. 760, pp. 110134. Date of Electronic Publication: 2024 Aug 23. - Publication Year :
- 2024
-
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.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Humans
Receptor, Transforming Growth Factor-beta Type II metabolism
Receptor, Transforming Growth Factor-beta Type II genetics
Promoter Regions, Genetic
Male
Transcriptional Activation
Signal Transduction
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Transcription, Genetic
Activating Transcription Factor 3 metabolism
Activating Transcription Factor 3 genetics
Wound Healing genetics
Fibroblasts metabolism
Collagen metabolism
Skin metabolism
Skin injuries
Skin pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 760
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 39181381
- Full Text :
- https://doi.org/10.1016/j.abb.2024.110134