Nan Zhang, Xin Yu, Wei Li, Kai Zhang, Jiaao Yu, Tongjun Liu
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Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury.</p><p><strong>Objective: </strong>In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-β1 signaling in wound healing of frostbite injury.</p><p><strong>Methods: </strong>sh-SOCS3 and sh-TGF-β1 were introduced to explore the biological role of SOCS3 in frostbite injury by detecting the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into the frostbitten mouse model in vivo.</p><p><strong>Results: </strong>Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-β1 to suppress the proliferation and migration of HSF cells, thus impeding the skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test (17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay (42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-β1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivo. ADSCs-EVs could promote frostbite wound healing by downregulating the expression of SOCS3 and upregulating the expression of TGF-β1 and collagen I.</p><p><strong>Conclusion: </strong>Collectively, ADSCs-EVs inhibit SOCS3 and facilitate the expression of TGF-β1, which promotes the proliferation and migration of HSF cells and subsequently enhances wound healing of frostbite injury.</p>","PeriodicalId":10979,"journal":{"name":"Current stem cell research & therapy","volume":"18 4","pages":"528-539"},"PeriodicalIF":2.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Extracellular Vesicles Derived from Adipose-Derived Stem Cells Facilitate Frostbite Wound Healing By Regulating SOCS3 Expression.\",\"authors\":\"Nan Zhang, Xin Yu, Wei Li, Kai Zhang, Jiaao Yu, Tongjun Liu\",\"doi\":\"10.2174/1574888X17666220715094504\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Though adipose-derived stem cells (ADSCs) have potential applications for the repair and regeneration of damaged tissues, limited studies have defined the function of ADSCs on dermal fibroblasts. Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury.</p><p><strong>Objective: </strong>In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-β1 signaling in wound healing of frostbite injury.</p><p><strong>Methods: </strong>sh-SOCS3 and sh-TGF-β1 were introduced to explore the biological role of SOCS3 in frostbite injury by detecting the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into the frostbitten mouse model in vivo.</p><p><strong>Results: </strong>Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-β1 to suppress the proliferation and migration of HSF cells, thus impeding the skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test (17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay (42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-β1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivo. 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引用次数: 2
摘要
背景:虽然脂肪源性干细胞(ADSCs)在损伤组织的修复和再生方面具有潜在的应用，但有限的研究已经确定了ADSCs对真皮成纤维细胞的功能。我们的RNA-seq测序鉴定了冻伤中SOCS3的差异表达。目的:在本研究中，我们旨在验证来自脂肪源性间充质干细胞(adscs - ev)的细胞外囊泡可能调节SOCS3/TGF-β1信号在冻伤创面愈合中的作用。方法:引入sh-SOCS3和sh-TGF-β1，通过检测小鼠皮肤成纤维细胞(HSF)的增殖、迁移及创面愈合情况，探讨SOCS3在冻伤损伤中的生物学作用。此外，提取的adscs - ev在体外与HSF细胞进行干扰，或注射到体内冻伤小鼠模型中。结果:冻伤小鼠皮肤组织中SOCS3表达上调。与sh-NC相比，sh-SOCS3在伤后第7天(31.34±4.35 vs 41.83±3.74,p < 0.05)和第14天(63.42±6.01 vs 88.99±5.12,p < 0.05)创面愈合率较高。沉默SOCS3可促进冻伤创面愈合。此外，SOCS3下调TGF-β1，抑制HSF细胞的增殖和迁移，从而阻碍皮肤创面愈合。CCK-8法、划痕法(17.82±4.25 vs 49.78±2.54,p < 0.05)、Transwell法(42.33±6.81 vs 91.33±7.02,p < 0.05)显示adscs - ev可促进HSF细胞的增殖和迁移，并可调节SOCS3/TGF-β1的表达。体内实验也证实了adscs - ev在冻伤创面愈合中的作用。adscs - ev可通过下调SOCS3的表达，上调TGF-β1和胶原i的表达来促进冻伤创面愈合。结论:adscs - ev共同抑制SOCS3，促进TGF-β1的表达，促进HSF细胞的增殖和迁移，从而促进冻伤创面愈合。
Extracellular Vesicles Derived from Adipose-Derived Stem Cells Facilitate Frostbite Wound Healing By Regulating SOCS3 Expression.
Background: Though adipose-derived stem cells (ADSCs) have potential applications for the repair and regeneration of damaged tissues, limited studies have defined the function of ADSCs on dermal fibroblasts. Our RNA-seq sequencing identified differentially expressed SOCS3 in frostbite injury.
Objective: In the current study, we aim to examine the hypothesis that extracellular vesicles derived from adipose-derived mesenchymal stem cells (ADSCs-EVs) may modulate SOCS3/TGF-β1 signaling in wound healing of frostbite injury.
Methods: sh-SOCS3 and sh-TGF-β1 were introduced to explore the biological role of SOCS3 in frostbite injury by detecting the proliferation and migration of human skin fibroblast (HSF) cells and the wound healing in mice. Furthermore, the extracted ADSCs-EVs were interfered with HSF cells in vitro or injected into the frostbitten mouse model in vivo.
Results: Upregulation of SOCS3 occurred in the skin tissues of frostbitten mice. Compared to sh-NC, the wound healing rate of sh-SOCS3 presented higher on day 7(31.34±4.35 vs 41.83±3.74, p < 0.05) and day 14 (63.42±6.01 vs 88.99±5.12, p < 0.05) after injury. Silencing SOCS3 can promote frostbite wound healing. Moreover, SOCS3 downregulated TGF-β1 to suppress the proliferation and migration of HSF cells, thus impeding the skin wound healing. Additionally, ADSCs-EVs could enhance the proliferation and migration of HSF cells according to the results of CCK-8 assay (p < 0.05), scratch test (17.82±4.25 vs 49.78±2.54, p < 0.05) and Transwell assay (42.33±6.81 vs 91.33±7.02, p < 0.05), and regulate the expression of SOCS3/TGF-β1. The role of ADSCs-EVs in frostbite wound healing was also confirmed in vivo. ADSCs-EVs could promote frostbite wound healing by downregulating the expression of SOCS3 and upregulating the expression of TGF-β1 and collagen I.
Conclusion: Collectively, ADSCs-EVs inhibit SOCS3 and facilitate the expression of TGF-β1, which promotes the proliferation and migration of HSF cells and subsequently enhances wound healing of frostbite injury.
期刊介绍：
Current Stem Cell Research & Therapy publishes high quality frontier reviews, drug clinical trial studies and guest edited issues on all aspects of basic research on stem cells and their uses in clinical therapy. The journal is essential reading for all researchers and clinicians involved in stem cells research.
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