Skin wound repairing effects of adipose mesenchymal stem cells is promoted by the combined application of insulin-like growth factor 1: The key role of miR-21-5p-mediated signaling transduction

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-09-23 DOI:10.1016/j.cyto.2024.156760

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Abstract

Mesenchymal stem cells (ADMSCs) have been applied to the treatment of skin injuries and the co-administration of cytokines can enhance the effects. In the current study, the promoting effects of insulin-like growth factor 1 (IGF-1) on the skin wound healing effects of adipose-derived MSCs (ADMSCs) were assessed and the associated mechanism was explored by focusing on miR-21-5p mediated pathways. ADMSCs were isolated from epididymis rats, and skin wounded rats were employed as the in vivo model for evaluating the effect of ADMCs on skin healing and secretion of cytokines. Then a microarray assay was employed to select potential miR target of IGF-1 on ADMSCs. The level of the selected miR was modulated in ADMSCs, and the effects on skin injuries were also assessed. Administration of ADMSCs promoted skin wound healing and induced the production of bFGF, IL-1β, PDGF, SDF-1, IGF-1, and TNF-α. The co-administration of IGF-1 and ADMSCs strengthened the effect of ADMSCs on skin wound by suppressing activity of matrix metalloproteinase-1 (MMP-1). At molecular level, the treatment of IGF-1 up-regulated miR-21-5p level in ADMSCs, which then suppressed the expression of KLF6 in injured skin tissues and promoted wound healing. The inhibition of miR-21-5p counteracted the promoting effects of IGF-1 on the skin healing effects of ADMSCs. Findings outlined in the current study indicated that IGF-1 could promote the wound healing effects of ADMSCs by up-regulating miR-21-5p level.

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联合应用胰岛素样生长因子1促进脂肪间充质干细胞的皮肤伤口修复效应：miR-21-5p介导的信号转导的关键作用

间充质干细胞（ADMSCs）已被应用于治疗皮肤损伤，联合使用细胞因子可增强其效果。本研究评估了胰岛素样生长因子1（IGF-1）对脂肪间充质干细胞（ADMSCs）皮肤伤口愈合效果的促进作用，并通过关注miR-21-5p介导的途径探讨了相关机制。研究人员从附睾大鼠体内分离出 ADMSCs，并以皮肤损伤大鼠为体内模型，评估 ADMCs 对皮肤愈合和细胞因子分泌的影响。然后用芯片分析法筛选出 IGF-1 在 ADMSCs 上的潜在 miR 靶标。研究人员调节了所选 miR 在 ADMSCs 中的水平，并评估了其对皮肤损伤的影响。给予 ADMSCs 可促进皮肤伤口愈合，并诱导产生 bFGF、IL-1β、PDGF、SDF-1、IGF-1 和 TNF-α。通过抑制基质金属蛋白酶-1（MMP-1）的活性，IGF-1 和 ADMSCs 的联合应用加强了 ADMSCs 对皮肤伤口的作用。在分子水平上，IGF-1能上调ADMSCs中的miR-21-5p水平，进而抑制KLF6在受伤皮肤组织中的表达，促进伤口愈合。抑制 miR-21-5p 可抵消 IGF-1 对 ADMSCs 皮肤愈合作用的促进作用。本研究概述的结果表明，IGF-1 可通过上调 miR-21-5p 水平促进 ADMSCs 的伤口愈合作用。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.