1. Academic Validation
  2. HCV poly U/UC sequence-induced inflammation leads to metabolic disorders in vulvar lichen sclerosis

HCV poly U/UC sequence-induced inflammation leads to metabolic disorders in vulvar lichen sclerosis

  • Life Sci Alliance. 2021 Jun 18;4(8):e202000906. doi: 10.26508/lsa.202000906.
Qing Cong 1 Xiao Guo 1 Shengwei Zhang 1 Jinhui Wang 1 Yi Zhu 2 Lili Wang 1 Guangxing Lu 1 Yufeng Zhang 1 Wei Fu 1 Liying Zhou 1 Shuaikang Wang 1 Cenxi Liu 1 Jia Song 3 Chaoyong Yang 3 4 Chi Luo 2 Ting Ni 1 Long Sui 5 He Huang 6 Jin Li 7
Affiliations

Affiliations

  • 1 Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China.
  • 2 Institute of Environmental Medicine and Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 4 The Ministry of Education Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory for Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
  • 5 Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China [email protected].
  • 6 Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China [email protected].
  • 7 Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China [email protected].
Abstract

Vulvar lichen sclerosis (VLS) is a dermatologic disorder that affects women worldwide. Women with VLS have white, atrophic papules on the vulva. They suffer from life-long intense pruritus. Corticosteroids are the first-line of treatments and the most effective medicines for VLS. Although VLS has been speculated as an autoimmune disease for a long time, its pathogenesis and the molecular mechanism is largely unknown. We performed a comprehensive multi-omics analysis of paired samples from VLS patients as well as healthy donors. From the RNA-seq analysis, we found that VLS is correlated to abnormal antivirus response because of the presence of Hepatitis C Virus poly U/UC sequences. Lipidomic and metabolomic analysis revealed that inflammation-induced metabolic disorders of fatty acids and glutathione were likely the reasons for pruritus, atrophy, and pigment loss in the vulva. Thus, the present study provides an initial interpretation of the pathogenesis and molecular mechanism of VLS and suggests that metabolic disorders that affect the vulva may serve as therapeutic targets for VLS.

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