Membrane progesterone receptor α (mPRα/PAQR7) promotes migration, proliferation and BDNF release in human Schwann cell-like differentiated adipose stem cells

Mol Cell Endocrinol. 2021 Jul 1:531:111298. doi: 10.1016/j.mce.2021.111298. Epub 2021 Apr 27.

Abstract

Membrane progesterone receptors (mPRs) were recently found to be present and active in Schwann cells, where they have a potentially pro-regenerative activity. In this study, we investigated the role of mPRs in human adipose stem cells (ASC) differentiated into Schwann cell-like cells (SCL-ASC), which represent a promising alternative to Schwann cells for peripheral nerve regeneration. Our findings show that mPRs are present both in undifferentiated and differentiated ASC, and that the differentiation protocol upregulates mPR expression. Activation of mPRα promoted cell migration and differentiation in SCL-ASC, alongside with changes in cell morphology and mPRα localization. Moreover, it increased the expression and release of BDNF, a neurotrophin with pro-regenerative activity. Further analysis showed that Src and PI3K-Akt signaling pathways are involved in mPRα activity in SCL-ASC. These findings suggest that mPRα could play a pro-regenerative role in SCL-ASC and may be a promising target for the promotion of peripheral nerve regeneration.

Keywords: Adipose stem cells; Brain-derived neurotrophic factor; Cell migration; Cell proliferation; Membrane progesterone receptor α; Peripheral nerve regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Primary Cell Culture
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Progesterone / genetics*
  • Receptors, Progesterone / metabolism*
  • Regeneration
  • Schwann Cells / cytology*
  • Schwann Cells / metabolism
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Up-Regulation

Substances

  • Brain-Derived Neurotrophic Factor
  • Receptors, G-Protein-Coupled
  • Receptors, Progesterone
  • membrane progestin receptor alpha, human
  • BDNF protein, human