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TMEM88 mediates inflammatory cytokines secretion by regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway in LX-2 cells

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Abstract

Recent data have shown that Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane, interacts with the PDZ domain of disheveled-1 (Dvl-1) in Xenopus embryos. Indeed, TMEM88 might inhibit the canonical Wnt/β-catenin signaling pathway by competing with LRP5/6 for interaction with Dvl-1. TMEM88 plays a crucial role in regulating human stem cell differentiation and embryonic development. Until recently, the function of TMEM88 has been a matter of debate. In this study, we explore the role of TMEM88 in cytokine secretion and the role of the MAPK and Wnt/β-catenin signaling pathway in tumor necrosis factor-alpha (TNF-α)-induced TMEM88 expression in LX-2 cells. We demonstrated that overexpression of TMEM88 results in an upregulation of IL-6 and IL-1β secretion. On the other hand, knockdown of TMEM88 by transfecting siRNA decreased IL-6 and IL-1β secretion in LX-2 cells. Meanwhile, the results showed that TMEM88 silencing could increase the expression levels of canonical Wnt/β-catenin accompanied with upregulated phosphorylation of wnt3a, wnt10b and β-catenin protein levels in response to TNF-α. In conclusion, these results indicated that TMEM88 plays a significant role in TNF-α-enhanced cytokine (IL-6 and IL-1β) secretion of LX-2 cells via regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (Nos. 81700522, 81470003), the Provincial Natural Science Research Project of Colleges and Universities of Anhui Province (No. KJ2016A348), the fund of Anhui medical university doctoral start research (No. 0601067101), Anhui Medical University early contact research of clinical medicine(2015-ZQKY-47), Guangdong Province Science and Technology Project (2013B021800164), Sichuan Medical Law Research Center(YF16-Y22) and Humanities and Social Science Research Project of Colleges and Universities of Anhui Province (No. SK2016A0482).

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  1. Tao Xu and Lin-xin Pan contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China

    Tao Xu, Xiao-ming Meng, Cheng Huang & Jun Li

  2. Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China

    Tao Xu, Xiao-ming Meng, Cheng Huang & Jun Li

  3. School of Life Sciences, Anhui Medical University, Hefei, 230032, China

    Lin-xin Pan

  4. Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, 100850, China

    Yun-xuan Ge

  5. Department of Medical, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China

    Peng Li

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  1. Tao Xu
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  2. Lin-xin Pan
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  3. Yun-xuan Ge
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Correspondence to Jun Li.

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Xu, T., Pan, Lx., Ge, Yx. et al. TMEM88 mediates inflammatory cytokines secretion by regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway in LX-2 cells. Inflammopharmacol 26, 1339–1348 (2018). https://doi.org/10.1007/s10787-017-0419-z

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  • DOI: https://doi.org/10.1007/s10787-017-0419-z

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