RESUMO
Current gold standard for the replacement of small-diameter blood vessel (ID < 4 mm) is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts (SDVG) on weak endothelialization, intimal hyperplasia and low patency. Herein, we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling. The engineered endothelial cell vesicles were modified with azide groups (ECVs-N3) through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry, and thus fabricating ECVG (ECVs-N3 modified SDVG), which assists inhibition of platelet adhesion and activation, promotion of ECs adhesion and enhancement of anti-inflammation. Furthermore, In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL, and the tailored endothelialization enabled to convert endothelial cells (ECs) into some specific ECs clusters. One of the specific cluster, Endo_C5 cluster, was only detected in ECVG. Consequently, our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells, and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.
RESUMO
BACKGROUND: Cancer-associated fibroblasts (CAFs) and their secretion, C-X-C motif chemokine ligand 12 (CXCL12), play an important role in the development of lung adenocarcinoma (LUAD). Interleukin 17A (IL-17A) is also crucial in regulating tumor progression. Herein, we explored the specific relationships between these two factors and their mechanisms in the progression of LUAD. METHODS: Immunohistochemistry was utilized to assess the differential expression levels of IL-17A and CXCL12 in tumor versus normal tissues of LUAD patients, followed by gene correlation analysis. Cell counting kit-8 (CCK8), wound-healing and transwell assays were performed to investigate the effect of IL-17A on the function of LUAD cells. qPCR, immunofluorescence, immunohistochemistry and western blot analyses were conducted to elucidate the potential mechanism by which IL-17A facilitates the development of LUAD via CXCL12. Male BALB-C nude mice were used to explore the role of IL-17A in subcutaneous LUAD mouse models. RESULTS: Elevated expression levels of IL-17A and CXCL12 were observed in LUAD tissues, exhibiting a positive correlation. Further studies revealed that IL-17A could stimulate CAFs to enhance the release of CXCL12, thereby facilitating the growth, proliferation, and metastasis of LUAD. The binding of CXCL12 to its specific receptor influences the activation of the Wnt/ß-Catenin pathway, which in turn affects the progression of LUAD. In vivo experiments have demonstrated that IL-17A enhances the growth of LUAD tumors by facilitating the secretion of CXCL12. Conversely, inhibiting CXCL12 has been demonstrated to impede tumor growth. CONCLUSIONS: We discovered that IL-17A promotes the release of CAFs-derived CXCL12, which in turn facilitates the development of LUAD via the Wnt/ß-Catenin signaling pathway.