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Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 151–158 | Cite as

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

  • Junqin Liang
  • Xuewen Zeng
  • Yilinuer Halifu
  • Wenjing Chen
  • Fengxia Hu
  • Peng Wang
  • Huan Zhang
  • Xiaojing Kang
Article

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.

Keywords

Pemphigus vulgaris (PV) RhoA/ROCK signaling Oxidative stress Apoptosis Inflammatory response 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Junqin Liang
    • 1
  • Xuewen Zeng
    • 2
  • Yilinuer Halifu
    • 1
  • Wenjing Chen
    • 1
  • Fengxia Hu
    • 1
  • Peng Wang
    • 1
  • Huan Zhang
    • 1
  • Xiaojing Kang
    • 1
  1. 1.Department of DermatologyPeople’s Hospital of Xinjiang Uygur Autonomous RegionUrumchiPeople’s Republic of China
  2. 2.Department of Plastic SurgeryPeople’s Hospital of Xinjiang Uygur Autonomous RegionUrumchiPeople’s Republic of China

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