期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 4, 页码 1949-1957出版社
WILEY
DOI: 10.1111/jcmm.15931
关键词
adipocyte differentiation; autophagy; Graves' orbitopathy; inflammation; Neferine; oxidative stress
资金
- 2018-2020 Three-year Action Plan for Traditional Chinese Medicine Further Development in Shanghai [ZY2018-2020-CCCX-2002-08]
- Shanghai Committee of Science and Technology Research Projects [19140904600, 18401900800]
- National Natural Science Foundation of China [81373617, 81072793]
Previous studies have shown that inhibition of autophagy suppresses adipogenic differentiation in Graves' orbitopathy (GO) patient-derived fibroblasts. Neferine, extracted from Nelumbo nucifera, has been found to inhibit autophagy and up-regulate Nrf2 expression. In this study, neferine was shown to suppress IL-13-induced autophagy, inflammation, fibrosis, and adipogenic differentiation in GO patient-derived orbital fibroblasts, suggesting a potential therapeutic role for neferine in GO.
Previous studies in Graves' orbitopathy (GO) patient-derived fibroblasts showed that inhibition of autophagy suppresses adipogenic differentiation. Autophagy activation is associated with inflammation, production of reactive oxygen species and fibrosis. Neferine is an alkaloid extracted from Nelumbo nucifera, which induces Nrf2 expression and inhibits autophagy. Here, we have elucidated the role of neferine on interleukin (IL)-13-induced autophagy using patient-derived orbital fibroblasts as an in vitro model of GO. GO patient-derived orbital fibroblasts were isolated and cultured to generate an in vitro model of GO. Autophagy was determined by Western blot detection of the markers such as Beclin-1, Atg-5 and LC3 and by immunofluorescence detection of autophagosome formation. Analysis of differentiation towards an adipogenic lineage was performed by Oil red O staining. The expression of inflammatory factors was detected by ELISA and semiquantitative RT-PCR. Neferine inhibited autophagy in GO orbital fibroblasts, as indicated by the suppression of IL-13-induced autophagosome formation, overexpression of autophagy markers, increased LC3-II/LC3-I levels and finally down-regulation of p62. Neferine suppressed IL-13-induced inflammation, ROS generation, fibrosis and adipogenic differentiation in GO patient-derived orbital fibroblasts. The anti-inflammatory, antioxidant and antiadipogenic effects of neferine were accompanied by the up-regulation of Nrf2. These results indicated that orbital tissue remodelling and inflammation in GO may be mediated by autophagy, and neferine suppressed autophagy-related inflammation and adipogenesis through a mechanism involving Nrf2.
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