Open Access

ARTICLE

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

by LEI FU¹, JINGWEN JIANG², XUEWU CHEN², FENGTING ZHU², HUI ZHANG^2,*

1 Department of Dermatology, Hainan Hospital of Traditional Chinese Medicine, Haikou, 570203, China
2 Department of Oncology, Hainan Hospital of Traditional Chinese Medicine, Haikou, 570203, China

* Address correspondence to: Hui Zhang,

BIOCELL 2022, 46(5), 1289-1297. https://doi.org/10.32604/biocell.2022.016726

Received 20 March 2021; Accepted 07 July 2021; Issue published 06 January 2022

Abstract

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.

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