Progranulin promotes proliferation, migration and invasion via the PI3K/Akt signalling pathway in a model of endometriosis

Reprod Biomed Online. 2023 Mar;46(3):425-435. doi: 10.1016/j.rbmo.2022.11.006. Epub 2022 Nov 18.

Abstract

Research question: What are the levels of progranulin (PGRN) expression in primary endometrial stromal cells (ESC) and endometrial tissue in patients with endometriosis (EMS)? What is the role and mechanism of action of PGRN in EMS?

Design: Endometrial tissue was collected from 30 patients, 15 with EMS (EMS group) and 15 without EMS (non-EMS group). PGRN expression in endometrial tissue and ESC was analysed by immunohistochemistry, immunofluorescence, western blotting and quantitative reverse transcription polymerase chain reaction. PGRN overexpression and silencing ESC were established with lentivirus to detect the effect on proliferation, invasion and migration. The relationship between PGRN and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signalling pathway was verified by western blotting. A rescue assay was performed with PI3K inhibitor treatment.

Results: The PGRN expression was significantly higher in EMS samples. PGRN up-regulation promoted proliferation (P = 0.007), migration (P = 0.002) and invasion (P < 0.001) of eutopic endometrial stromal cells (EUESC). The ratio of p-AKT/AKT was higher in the overexpression PGRN (ovPGRN) group than in the overexpression-NC (ovNC) group (P = 0.004). Silencing PGRN produced the opposite results, and LY2940002 addition reversed the effect of PGRN up-regulation on the proliferation, invasion and migration of EUESC.

Conclusions: PGRN might promote the proliferation, invasion and migration of EUESC via the PI3K/Akt signalling pathway. These preliminary in-vitro findings may present a new perspective and inspire further study of the mechanism of EMS.

Keywords: Endometriosis; Invasion; Migration; Primary eutopic endometrial stromal cells.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Endometriosis* / metabolism
  • Endometrium / metabolism
  • Female
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Progranulins / metabolism
  • Progranulins / pharmacology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Stromal Cells / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Progranulins