Sortilin regulates keratinocyte proliferation and apoptosis through the PI3K-AKT signaling pathway

Life Sci. 2021 Aug 1:278:119630. doi: 10.1016/j.lfs.2021.119630. Epub 2021 May 15.

Abstract

Sortilin is found to regulate proliferation and death of different cells, while its role in regulating keratinocyte proliferation and apoptosis is still unknown. In this study, we found that sortilin levels significantly increased in psoriasis patients, and sortilin suppression eliminated the proliferation of HaCaT cells induced by M5 cocktail solution and enhanced the levels of cleaved caspase 3 protein and the Bax/Bcl-2 ratio; however, levels of p-PI3K and p-AKT were decreased. In addition, sortilin silencing remitted the characteristic changes associated with psoriasis-like skin lesions. In summary, suppressed sortilin expression helped inhibit keratinocyte proliferation in HaCaT cells by inactivating PI3K/AKT signaling, which provides a new target for the therapy of psoriasis.

Keywords: Keratinocytes; PI3K/AKT signaling; Psoriasis; Sortilin.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / pharmacology*
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Apoptosis*
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Psoriasis / drug therapy
  • Psoriasis / metabolism
  • Psoriasis / pathology*
  • Young Adult

Substances

  • Adaptor Proteins, Vesicular Transport
  • Proto-Oncogene Proteins c-akt
  • sortilin