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Knockdown of H19 Inhibits the Pathogenesis of Acne Vulgaris by Targeting the miR-196a/TLR2/NF-κB Axis

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Abstract

Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit, and Propionibacterium acnes (P. acnes) has been implicated in acne inflammation. Numerous studies have shown that non-coding RNAs play important roles in regulating the pathophysiological processes of acne. In addition, the first imprinted long non-coding RNA (lncRNA) identified, H19, plays a critical role in inflammatory disease. However, the expression and role of H19 in AV remain unclear. In this study, we investigated the effects of H19 in keratinocytes and explored the regulatory mechanisms underlying these effects. H19 was upregulated in keratinocytes treated with P. acnes in a concentration-dependent manner. The phosphorylated forms of the nuclear factor (NF)-κB-related proteins IκBα (p-IκBα) and p65 (p-P65) were significantly upregulated after P. acnes treatment. Additionally, secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 was upregulated in a concentration-dependent manner. Knockdown of H19 inhibited the expression of p-IκBα and p-P65 as well as the secretion of TNF-α, IL-6, and IL-8 in keratinocytes treated with P. acnes. Moreover, H19 was found to exert its proinflammatory effects by activating NF-κB. H19, which was localized mainly in the cytoplasm of keratinocytes, facilitated Toll-like receptor 2 (TLR2) expression by acting as a miR-196a sponge. H19 thus promoted the activation of NF-κB and the secretion of inflammatory cytokines through the miR-196a/TLR2 axis. These findings provide novel insight into the pathogenesis of AV.

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Funding

This work was supported by the National Science Foundation of China (Nos. 81960563 and 81760559).

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Author notes

  1. Shuyun Yang, Fumin Fang and Tingting Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, The People’s Hospital of Baoshan, Baoshan, Yunnan, China

    Shuyun Yang

  2. Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China

    Fumin Fang, Xiuqin Yu, Changzhi Yang, Xiaoping Zhang, Lu Wang, Liping Zhu, Kai Shao & Tingting Zhu

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  1. Shuyun Yang
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Correspondence to Tingting Zhu.

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Yang, S., Fang, F., Yu, X. et al. Knockdown of H19 Inhibits the Pathogenesis of Acne Vulgaris by Targeting the miR-196a/TLR2/NF-κB Axis. Inflammation 43, 1936–1947 (2020). https://doi.org/10.1007/s10753-020-01268-z

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