PGRN Suppresses Inflammation and Promotes Autophagy in Keratinocytes Through the Wnt/β-Catenin Signaling Pathway

Rong Tian, You Li, Xu Yao

Research output: Contribution to journalArticle

Abstract

Psoriasis is a chronic, immune-mediated inflammatory skin disease that has a major impact on patients’ quality of life. Progranulin (PGRN) is highly expressed in skin diseases and plays an important role in inflammation response and autophagy. However, the function of PGRN in the immune system and autophagy in psoriasis has not been clearly identified and elaborated on. Thus, this study aimed to investigate the role of PGRN on the inflammatory and autophagy process underlying inflammation in HaCaT cells. We showed that PGRN was markedly highly expressed in psoriasis lesions and inflammatory HaCaT cells. Specific silencing of PGRN promoted the production of the inflammatory cytokines IL-1β, IL-6, COX-2, iNOs, and MCP-1. Furthermore, PGRN siRNA promoted autophagy-related gene p62 and suppressed LC3II and Atg7 in HaCaT cells, while overexpression of PGRN showed a contrary effect. Moreover, knockdown of PGRN upregulated the expression levels of β-catenin, cyclin D1, and c-myc proteins. Finally, we demonstrated that IWP-2, an inhibitor of the Wnt/β-catenin signaling pathway, stemmed the pro-inflammatory and anti-autophagy effect of PGRN siRNA in TNF-α-treated HaCaT cells. Collectively, our findings suggest that PGRN is upregulated in psoriasis lesions and that the overexpression of PGRN inhibits the inflammation in keratinocytes induced by TNF-α by negatively regulating the production of inflammatory factors and positively mediating autophagy through the Wnt/β-catenin signaling pathway; this indicated that overexpression of PGRN may be a potential therapeutic option in psoriasis.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalInflammation
DOIs
StateAccepted/In press - May 30 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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