Department of Burn and Plastic Surgery, Zhenjiang First People's Hospital, Zhenjiang City, Jiangsu, China.
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
J Cosmet Dermatol. 2024 Apr;23(4):1404-1416. doi: 10.1111/jocd.16117. Epub 2024 Jan 30.
Keloid represents a benign skin tumor with many cancer-like features. Extracellular vesicles (EVs) derived from human adipose-derived stem cells (hADSCs) play a role in cell migration of multiple diseases.
This study aimed to investigate the impact of hADSC-EVs on human keloid fibroblasts (HKFs).
hADSCs were cultured to the 3rd generation, and subsequently assessed for their osteogenic, adipogenic, and chondrogenic differentiative abilities using flow cytometry, alizarin red, oil red O, and alcian blue staining techniques. hADSC-EVs were isolated through ultracentrifugation and subsequently identified. HKFs at the 3rd generation were subjected to treatment with hADSC-EVs to observe their endocytosis of EVs by immunofluorescence. CCK-8, wound healing, and Transwell assays were performed to test HKF proliferation and migration. The levels of autophagy proteins, collagens, and Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3) were determined through Western blot analysis. Suppressor of cytokine signaling 1 (SOCS1) expression was determined by RT-qPCR and Western blot.
hADSC-EVs were successfully isolated from hADSCs. PKH67-labeled hADSC-EVs were observed to be endocytosed by HKFs, resulting the inhibition of HKF proliferation, migration, as well as a reduction in collagen deposition. hADSC-EVs carried SOCS1 into HKFs to suppress HKF autophagy. SOCS1 downregulation in hADSC-EVs partially nullified the inhibitory effect of hADSC-EVs on HKFs. hADSC-EV-carried SOCS1 inhibited the activation of the JAK2/STAT3 pathway. JAK2/STAT3 pathway activation partially abrogated the suppression of hADSC-EVs on the proliferation, migration, and collagen deposition of HKF.
hADSC-EVs carried SOCS1 into HKFs and suppressed HKF autophagy, proliferation, migration, and collagen deposition by inactivating the JAK2/STAT3 pathway.
瘢痕疙瘩是一种具有许多癌症特征的良性皮肤肿瘤。人脂肪源性干细胞（hADSCs）来源的细胞外囊泡（EVs）在多种疾病的细胞迁移中发挥作用。
本研究旨在探讨 hADSC-EVs 对人瘢痕疙瘩成纤维细胞（HKFs）的影响。
培养第三代 hADSCs，并用流式细胞术、茜素红、油红 O 和阿利新蓝染色技术评估其成骨、成脂和成软骨分化能力。通过超速离心分离 hADSC-EVs，并进行鉴定。第三代 HKFs 用 hADSC-EVs 处理，通过免疫荧光观察 EVs 的内吞作用。通过 CCK-8、划痕愈合和 Transwell 测定法检测 HKF 的增殖和迁移。通过 Western blot 分析测定自噬蛋白、胶原蛋白、Janus 激酶 2（JAK2）和信号转导和转录激活因子 3（STAT3）的水平。通过 RT-qPCR 和 Western blot 测定抑制细胞因子信号转导 1（SOCS1）的表达。
成功从 hADSCs 中分离出 hADSC-EVs。PKH67 标记的 hADSC-EVs 被观察到被 HKFs 内吞，导致 HKF 增殖、迁移减少，胶原沉积减少。hADSC-EVs 将 SOCS1 带入 HKFs 以抑制 HKF 自噬。hADSC-EVs 中 SOCS1 的下调部分消除了 hADSC-EVs 对 HKFs 的抑制作用。hADSC-EV 携带的 SOCS1 抑制了 JAK2/STAT3 通路的激活。JAK2/STAT3 通路的激活部分消除了 hADSC-EVs 对 HKF 增殖、迁移和胶原沉积的抑制作用。
hADSC-EVs 将 SOCS1 带入 HKFs，并通过失活 JAK2/STAT3 通路抑制 HKF 自噬、增殖、迁移和胶原沉积。
