Affiliation:
1. Department of Burn and Plastic Surgery Zhenjiang First People's Hospital Zhenjiang City Jiangsu China
2. Jiangsu Key Laboratory of Medical Science and Laboratory Medicine Institute of Stem Cell, School of Medicine, Jiangsu University Zhenjiang Jiangsu China
Abstract
AbstractBackgroundKeloid 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.AimsThis study aimed to investigate the impact of hADSC‐EVs on human keloid fibroblasts (HKFs).MethodshADSCs 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.ResultshADSC‐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.ConclusionhADSC‐EVs carried SOCS1 into HKFs and suppressed HKF autophagy, proliferation, migration, and collagen deposition by inactivating the JAK2/STAT3 pathway.