Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

Jinxiu Yang; Shiyi Li; Leren He; Minliang Chen

doi:10.1093/burnst/tkab020

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Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

更新时间：2022-06-14

- Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 作者机构：
  
  1. Department of Burn and Plastic Surgery
  2. Chinese People’s Liberation Army General Hospital
  3. 7th Department of Plastic Surgery
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkab020
  CLC：
- Published：2021，
  
  Published Online：11 September 2021，
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Jinxiu Yang, Shiyi Li, Leren He, Minliang Chen, Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine, Burns & Trauma, Volume 9, 2021, tkab020, https://doi.org/10.1093/burnst/tkab020
DOI：

Jinxiu Yang, Shiyi Li, Leren He, Minliang Chen, Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine, Burns & Trauma, Volume 9, 2021, tkab020, https://doi.org/10.1093/burnst/tkab020 DOI：

摘要

Abstract

BackgroundThe clinical features of keloids consist of aberrant proliferation

secretion

differentiation and apoptosis of keloid dermis-derived fibroblasts (KFBs). Notably

the apoptosis rate of KFBs is lower than the proliferation rate. Though the anti-fibrotic effect of adipose-derived stem cells (ADSCs) on keloids has become a hot topic of research

the exact anti-fibrotic mechanism of the paracrine effect remains unclear. This study aimed to find out how the conditioned medium of ADSCs (ADSC-CM) exerts an anti-fibrotic effect in KFBs.MethodsKFBs and ADSCs were extracted and cultured. Then

ADSC-CM was prepared. Whether ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8

an 5-Ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. The expressions of cyclooxygenase-1 (COX-1)

COX-2

caspase 3 and B-cell lymphoma-2 (Bcl-2) in ADSC-CM-cultured KFBs were tested by real-time PCR and western blotting. To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis

a specific COX-2 inhibitor

celecoxib

was applied to KFBs cultured in ADSC-CM. Moreover

we tested the production of arachidonic acid (AA) and prostaglandin E2 (PGE2) by ELISA. Then

we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo.ResultsThe proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased. Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs. Furthermore

ADSC-CM strikingly elevated COX-2 mRNA and protein expressions

but COX-1 expression was unaltered. COX-2 inhibitors reduced ADSC-CM-induced apoptosis. Additionally

COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression. ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition. In the nude mouse model

expressions of AA

COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls.ConclusionsWe showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM. By employing a specific COX-2 inhibitor

COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects.

关键词

Keywords

KeloidsAdipose-derived stem cellsFibroblastsApoptosisAnti-fibrosis cyclooxygenase-2Arachidonic acid

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