CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway

Yu Xin; Peiru Min; Heng Xu; Zheng Zhang; Yan Zhang; Yixin Zhang

doi:10.1093/burnst/tkaa025

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CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway

更新时间：2022-06-09

- CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway
- Burns & Trauma Vol. 8, Issue 1, (2020)
- 作者机构：
  
  Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkaa025
  CLC：
- Published：2020，
  
  Published Online：30 October 2020，
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Yu Xin, Peiru Min, Heng Xu, Zheng Zhang, Yan Zhang, Yixin Zhang, CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway, Burns & Trauma, Volume 8, 2020, tkaa025, https://doi.org/10.1093/burnst/tkaa025
DOI：

Yu Xin, Peiru Min, Heng Xu, Zheng Zhang, Yan Zhang, Yixin Zhang, CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway, Burns & Trauma, Volume 8, 2020, tkaa025, https://doi.org/10.1093/burnst/tkaa025 DOI：

摘要

Abstract

BackgroundKeloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion. These pathological behaviours may be related to the heterogeneity of keloid fibroblasts (KFs); however

because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism. Our previous studies revealed that the expansion of CD26+ KFs was responsible for increased keloid proliferation and invasion capabilities; the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation. The aim of this study was to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities

and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target.MethodsFlow cytometry was performed to isolate CD26+/CD26− fibroblasts from KFs and normal fibroblasts. To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor (IGF-1R)

lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection. Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. Scratching assay and transwell assay were used to assess cell migration and invasion abilities. To further quantify the regulatory role of CD26 expression in the relevant signalling pathway

RT-qPCR

western blot

ELISA

PI3K activity assay and immunofluorescence were used.ResultsAberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs. Furthermore

the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion. The PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein.ConclusionsCD26 can be the effective biomarker for KFs

and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway. This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.

关键词

Keywords

CD26IGF-1InvasionKeloidsPI3K/AKT/mTOR signalling pathwayProliferationFibroblast

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