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脂肪源干细胞外泌体通过调节 Th17/Treg 细胞平衡抑制肥厚性瘢痕形成。

Adipose-Derived Stem Cell Exosomes Inhibit Hypertrophic Scaring Formation by Regulating Th17/Treg Cell Balance.

机构信息

Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Biomed Res Int. 2022 Oct 12;2022:9899135. doi: 10.1155/2022/9899135. eCollection 2022.

Abstract

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-, and transcriptional factors of RORt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-, RORt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4 T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-, and RORt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-, and RORt; and increased IL-10 and Foxp3 production.

摘要

为了揭示 ADCS-Exos 在炎症因子分泌、Th17 和调节性 T(Treg)细胞从幼稚 CD4+T 细胞分化中的作用,探索了其在肥厚性瘢痕形成和成熟中的作用。通过 ELISA、qRT-PCR 和免疫印迹法检测了 ADCS-Exos 处理或未处理的患者瘢痕组织和小鼠创面模型中的局部炎症因子 IL-6、IL-10、IL-17A 和 TNF-,以及转录因子 RORt 和 Foxp3。通过免疫组织化学染色和免疫印迹法检测了体外和体内细胞外基质(ECM)的沉积。结果表明,与萎缩性瘢痕和正常皮肤相比,肥厚性瘢痕中 IL-6、IL-10、IL-17A、TNF-、RORt 和 Foxp3 的 mRNA 和蛋白水平均升高。体外用 ADCS-Exos 处理的幼稚 CD4 T 细胞在 mRNA 和蛋白水平上产生的 IL-6、IL-17A、TNF-和 RORt 明显减少,而产生的 IL-10 和 Foxp3 明显增多。此外,ADSC-Exos 处理组的小鼠胶原沉积减少;IL-17A、TNF-和 RORt 减少;而 IL-10 和 Foxp3 产生增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/9581674/0fcd841feffb/BMRI2022-9899135.001.jpg

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