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Blocking RhoA/ROCK inhibits the pathogenesis of pemphigus vulgaris by suppressing oxidative stress and apoptosis through TAK1/NOD2-mediated NF-κB pathway

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Abstract

Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein. The release of inflammatory mediators TNF-α, IL-1β, and IL-6 was also attenuated. Mechanically, we observed that blockage of RhoA/ROCK repressed the TAK1/NOD2-mediated NF-κB pathway in HaCaT cells exposed to UVB. Taken together, these data reveal that RhoA/ROCK signaling is one of the regulators contributing to oxidative damage and apoptosis in human keratinocytes, suggesting that RhoA/ROCK signaling has strong potential to be used as a useful therapeutic target in skin diseases including PV.

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Acknowledgements

This research was supported by the CMA-L’ OREAL CHINA SKIN GRANT 2018 APPLICATION FORM (S2018151101).

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Author notes

  1. Junqin Liang and Xuewen Zeng have contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, NO. 91 Tianchi Road, Urumchi, 830001, Xinjiang Uygur Autonomous Region, People’s Republic of China

    Junqin Liang, Yilinuer Halifu, Wenjing Chen, Fengxia Hu, Peng Wang, Huan Zhang & Xiaojing Kang

  2. Department of Plastic Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, 830001, Xinjiang Uygur Autonomous Region, People’s Republic of China

    Xuewen Zeng

Author notes

  1. Junqin Liang and Xuewen Zeng are Coauthors.

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    1. Junqin Liang
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    Liang, J., Zeng, X., Halifu, Y. et al. Blocking RhoA/ROCK inhibits the pathogenesis of pemphigus vulgaris by suppressing oxidative stress and apoptosis through TAK1/NOD2-mediated NF-κB pathway. Mol Cell Biochem 436, 151–158 (2017). https://doi.org/10.1007/s11010-017-3086-x

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