2. Academic Validation
  3. C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes

C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes

  • Sci Rep. 2018 Jun 5;8(1):8590. doi: 10.1038/s41598-018-26996-z.
Caifeng Chen 1,  Na Wu 2,  Qiqi Duan 1,  Huizi Yang 3,  Xin Wang 1,  Peiwen Yang 1,  Mengdi Zhang 1,  Jiankang Liu 3,  Zhi Liu 4,  Yongping Shao 5,  Yan Zheng 6
Affiliations

Affiliations

  • 1 Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
  • 2 Department of Dermatology, Shaanxi Provincial People's Hospital, Xi'an, China.
  • 3 Frontier of institute of science and technology and Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
  • 4 Department of Dermatology, University of North Carolina, Chapel Hill, NC, USA.
  • 5 Frontier of institute of science and technology and Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. [email protected].
  • 6 Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. [email protected].
PMID: 29872130 DOI: 10.1038/s41598-018-26996-z
Abstract

Psoriasis is a chronic, relapsing inflammatory skin disease. The pathogenesis of psoriasis is complex and has not been fully understood. C10orf99 was a recently identified human antimicrobial peptide whose mRNA expression is elevated in psoriatic human skin samples. In this study, we investigated the functional roles of C10orf99 in epidermal proliferation under inflammatory condition. We showed that C10orf99 protein was significantly up-regulated in psoriatic skin samples from patients and the ortholog gene expression levels were up-regulated in imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Using M5-stimulated HaCaT cell line model of inflammation and a combinational approach of knockdown and overexpression of C10orf99, we demonstrated that C10orf99 could promote keratinocyte proliferation by facilitating the G1/S transition, and the pro-proliferation effect of C10orf99 was associated with the activation of the ERK1/2 and NF-κB but not the Akt pathways. Local depletion of C10orf99 by lentiviral vectors expressing C10orf99 shRNA effectively ameliorated IMQ-induced dermatitis. Taken together, these results indicate that C10orf99 plays a contributive role in psoriasis pathogenesis and may serve as a new target for psoriasis treatment.

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