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脂肪组织来源的无膜干细胞成分对角质形成细胞皮肤炎症的抑制作用

Inhibitory effect of membrane‑free stem cell components derived from adipose tissues on skin inflammation in keratinocytes.

作者信息

Ha Sang Eun, Vetrivel Preethi, Kim Seong Min, Bhosale Pritam Bhagwan, Kim Hun Hwan, Pak Jung Eun, Heo Jeong Doo, Kim Young Sil, Kim Gon Sup

机构信息

Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam‑do 52828, Republic of Korea.

T‑Stem Co., Ltd., Changwon, Gyeongsangnam‑do 51573, Republic of Korea.

出版信息

Mol Med Rep. 2022 Apr;25(4). doi: 10.3892/mmr.2022.12641. Epub 2022 Feb 16.

DOI:10.3892/mmr.2022.12641
PMID:35169867
Abstract

Inflammatory disorders of the skin are major public health concerns due to constant exposure to external stimuli. Skin cells are associated with prominent immune mechanisms to defend against adverse reactions. In the present study, the anti‑inflammatory properties of membrane‑free stem cell components (MFSCC) from adipose tissue‑derived stem cells (ADSCs) and their basic preventive effects on skin wrinkle formation using human keratinocytes (HaCaT) and fibroblast (Detroit 551) cells, were investigated. Initially, a human inflammation antibody array was used on tumor necrosis factor‑α (TNF‑α)/interferon‑γ (IFN‑γ)‑induced and MFSCC‑treated HaCaT cells. Array spots revealed three differential proteins, interleukin (IL)‑1 F1 (IL‑1α), IL‑6, and TIMP2. Of these three proteins, IL‑6 was significantly downregulated by MFSCC treatment. Western blot analysis revealed that IL‑6 and its key downstream proteins JAK2 and STAT3 were suppressed in MFSCC‑treated HaCaT cells. Further analysis revealed that MFSCC decreased the expression of TNF‑α/IFN‑γ‑induced phosphorylated (p)‑IκB‑α, p‑p65, p‑JNK, p‑ERK, and p‑p38 by inhibiting the activation of MAPK and NF‑κB pathways. Treatment of Detroit 551 cells with MFSCC increased COL1A1 and elastin but suppressed matrix metalloproteinase (MMP)‑1 and MMP‑8 protein expression levels. Collectively, these data indicated that MFSCC exhibited a primary inhibitory effect on inflammation and wrinkle formation in skin. These results provide a basis for further extensive studies and application of MFSCC in treating skin inflammatory disorders.

摘要

由于持续暴露于外部刺激,皮肤炎症性疾病是主要的公共卫生问题。皮肤细胞与显著的免疫机制相关联,以抵御不良反应。在本研究中,研究了来自脂肪组织来源干细胞(ADSCs)的无膜干细胞成分(MFSCC)的抗炎特性及其对人角质形成细胞(HaCaT)和成纤维细胞(底特律551)细胞皮肤皱纹形成的基本预防作用。最初,在肿瘤坏死因子-α(TNF-α)/干扰素-γ(IFN-γ)诱导的和MFSCC处理的HaCaT细胞上使用人炎症抗体阵列。阵列斑点显示出三种差异蛋白,即白细胞介素(IL)-1 F1(IL-1α)、IL-6和TIMP2。在这三种蛋白中,MFSCC处理可使IL-6显著下调。蛋白质印迹分析显示,在MFSCC处理的HaCaT细胞中,IL-6及其关键下游蛋白JAK2和STAT3受到抑制。进一步分析表明,MFSCC通过抑制MAPK和NF-κB途径的激活,降低了TNF-α/IFN-γ诱导的磷酸化(p)-IκB-α、p-p65、p-JNK、p-ERK和p-p38的表达。用MFSCC处理底特律551细胞可增加COL1A1和弹性蛋白,但抑制基质金属蛋白酶(MMP)-1和MMP-8蛋白表达水平。总体而言,这些数据表明MFSCC对皮肤炎症和皱纹形成具有初步抑制作用。这些结果为进一步广泛研究和应用MFSCC治疗皮肤炎症性疾病提供了依据。

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