Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway

Shixin Zhao; Hengdeng Liu; Hanwen Wang; Xuefeng He; Jinming Tang; Shaohai Qi; Ronghua Yang; Julin Xie

doi:10.1093/burnst/tkad048

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Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway

更新时间：2024-04-19

- Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway
- Burns & Trauma Vol. 12, Issue 1, (2024)
- 作者机构：
  
  1. Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University
  2. Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-Sen University
  3. Department of Burn and Plastic Surgery
  4. South China University of technology
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad048
  CLC：
- Published：2024，
  
  Published Online：2 January 2024，
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Shixin Zhao, Hengdeng Liu, Hanwen Wang, Xuefeng He, Jinming Tang, Shaohai Qi, Ronghua Yang, Julin Xie, Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway, Burns & Trauma, Volume 12, 2024, tkad048, https://doi.org/10.1093/burnst/tkad048
DOI：

Shixin Zhao, Hengdeng Liu, Hanwen Wang, Xuefeng He, Jinming Tang, Shaohai Qi, Ronghua Yang, Julin Xie, Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway, Burns & Trauma, Volume 12, 2024, tkad048, https://doi.org/10.1093/burnst/tkad048 DOI：

摘要

Abstract

BackgroundHypertrophic scar (HS) is a common fibroproliferative skin disease that currently has no truly effective therapy. Given the importance of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) in hypertrophic scar formation

the development of therapeutic strategies for endogenous inhibitors against PIK3CA is of great interest. Here

we explored the molecular mechanisms underlying the protective effects of miR-203a-3p (PIK3CA inhibitor) against excessive scar.MethodsBioinformatic analysis

immunohistochemistry

immunofluorescence

miRNA screening and fluorescence in situ hybridization assays were used to identify the possible pathways and target molecules mediating HS formation. A series of in vitro and in vivo experiments were used to clarify the role of PIK3CA and miR-203a-3p in HS. Mechanistically

transcriptomic sequencing

immunoblotting

dual-luciferase assay and rescue experiments were executed.ResultsHerein

we found that PIK3CA and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway were upregulated in scar tissues and positively correlated with fibrosis. We then identified miR-203a-3p as the most suitable endogenous inhibitor of PIK3CA. miR-203a-3p suppressed the proliferation

migration

collagen synthesis and contractility as well as the transdifferentiation of fibroblasts into myofibroblasts in vitro

and improved the morphology and histology of scars in vivo. Mechanistically

miR-203a-3p attenuated fibrosis by inactivating the PI3K/AKT/mTOR pathway by directly targeting PIK3CA.ConclusionsPIK3CA and the PI3K/AKT/mTOR pathway are actively involved in scar fibrosis and miR-203a-3p might serve as a potential strategy for hypertrophic scar therapy through targeting PIK3CA and inactivating the PI3K/AKT/mTOR pathway.

关键词

Keywords

FibrosisHypertrophic scarmiRNAPhosphatidylinositol 3-kinase catalytic subunit alphaTransdifferentiationmiR-203a-3pPhosphatidylinositol 3-kinaseAKTmTOR

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