in vitro by reducing NLRP3 inflammasome activity">Downregulation of hsa_circ_0002198 inhibits keloid fibroblast activities in vitro by reducing NLRP3 inflammasome activity

[摘要] The levels of hsa circular RNA_0002198 (hsa_circ_0002198) have been found to be significantly upregulated in keloid dermal fibroblasts. However, the functional role of hsa_circ_0002198 in keloid fibroblasts and the underlying molecular mechanism for its effects have not been reported. In this study, the levels of hsa_circ_0002198 and nucleotide-binding and oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) expression in keloid scar tissues and adjacent normal skin tissues were determined by quantitative real-time PCR and western blotting, respectively. In vitro models of keloid tissue were created by culturing primary keloid fibroblasts obtained from patients. A series of functional experiments, including CCK-8 assays, Transwell assays, and ELISA assays were performed to analyze the functional role of hsa_circ_0002198/NLRP3. Our data showed that hsa_circ_0002198 and NLRP3 were upregulated in keloid scar tissues when compared with adjacent normal tissues. Knockdown of hsa_circ_0002198 expression significantly suppressed cell proliferation, migration, and invasion, and those effects could be partially reversed by forced NLRP3 overexpression in keloid fibroblasts. At the molecular level, knockdown of hsa_circ_0002198 downregulated the levels of Col I, α-SMA, and NLRP3 proteins, as well as the levels of TGF-β, IL-1ß, and IL-33, but upregulated caspase 3 expression in keloid fibroblasts. All those effects were partially reversed after NLRP3 overexpression. In conclusion, our results suggest hsa_circ_0002198 as a potential target for treating keloid lesions.

[学科分类] 仪器

[关键词] Keloid;Fibroblast;hsa_circ_0002198;NLRP3