Int J Med Sci 2020; 17(14):2087-2094. doi:10.7150/ijms.45765

Research Paper

Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes

Qian-Nan Jia1,2, Yue-Ping Zeng1,2✉

1. Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
2. National Clinical Research Center for Dermatologic and Immunologic diseases, Beijing, China.

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Citation:
Jia QN, Zeng YP. Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes. Int J Med Sci 2020; 17(14):2087-2094. doi:10.7150/ijms.45765. Available from http://www.medsci.org/v17p2087.htm

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Abstract

Interleukin (IL)-13 plays a key role in the pathogenesis of atopic dermatitis (AD). Our preliminary study demonstrated that forced expression of miR-143 could block IL-13-induced down-regulation of epidermal barrier related proteins in epidermal keratinocytes. As previous studies suggested that miR-143 expression was regulated by mammalian target of rapamycin (mTOR) signaling pathway, we investigated the mechanism of mTOR signaling pathway in the epidermal barrier dysfunction of AD. The HaCaT cells were stimulated by IL-13 and subsequently treated with rapamycin. The expression levels of miR-143, IL-13 receptor α1 (IL-13Rα1), p-mTOR, p-S6K1, p-Akt, and epidermal barrier related proteins were analyzed through RT-qPCR and/or western blotting. The current study showed that IL-13 increased the expression levels of p-mTOR, p-S6K1, and p-Akt, and that rapamycin blocked IL-13-induced down-regulation of miR-143, suppressed the IL-13Rα1 expression and up-regulated the expressions of filaggrin, loricrin, and involucrin in HaCaT cells. This study proposed that IL-13 could activate the mTOR signaling pathway, and confirmed the vital role of mTOR-miR-143 signaling axis in the pathogenesis of AD. It provided solid evidences regarding rapamycin as a potential effective therapeutic option in the management of AD.

Keywords: mTOR, atopic dermatitis, rapamycin, microRNA-143, IL-13