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

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.