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Progranulin promotes proliferation, migration, and invasion of eutopic endometrial stromal cells in patients with endometriosis via the PI3K/Akt signaling pathway

Published:November 17, 2022DOI:https://doi.org/10.1016/j.rbmo.2022.11.006

      Highlights

      • High-purity primary eutopic endometrial stromal cells were successfully isolated.
      • PGRN levels were significantly elevated in endometriosis tissue samples.
      • PGRN promoted the proliferation, migration, and invasion of eutopic endometrial stromal cells.
      • These effects are achieved via the PI3K/Akt signalling pathway.

      Abstract

      Research question

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

      Design

      : Endometrial tissue was collected from 30 patients, 15 with endometriosis (EMS group) and 15 without endometriosis (non-EMS group). PGRN expression in endometrial tissue and endometrial stromal cells (ESCs) was analysed by immunohistochemistry, immunofluorescence, western blotting, and quantitative reverse-transcription polymerase chain reaction. PGRN overexpression and silencing ESCs 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 endometriosis samples (P<0.05) and promoted proliferation (P<0.05), migration (P<0.05), and invasion (P<0.05) of eutopic endometrial stromal cells. The ratio of p-AKT/AKT was higher in the overexpression-PGRN (ovPGRN) group than in the overexpression-NC (ovNC) group (P<0.05). Silencing PGRN produced the opposite results, and LY2940002 addition reversed the effect of PGRN up-regulation on the proliferation, invasion, and migration of eutopic endometrial stromal cells (EUESCs).

      Conclusions

      : PGRN might promote the proliferation, invasion, and migration of EUESCs 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

      Abbreviations:

      EMS (Endometriosis), EU (eutopic endometrium from endometriosis patients), NE (eutopic endometrium from non-endometriosis patients), ESCs (endometrial stromal cells), EUESCs (endometrial stromal cells from endometriosis patients), NESCs (endometrial stromal cells from non-endometriosis patients), PGRN (Progranulin), ovPGRN (overexpression-PGRN), ovNC (overexpression-Negative Control), shPGRN (silenced-PGRN), shNC (silenced-Negative Control), IF (immunofluorescence), IHC (immunohistochemistry), B PI3K/Akt (phosphatidylinositol-3-kinase/protein kinase), PGRN (progranulin), qRT-PCR (quantitative real-time polymerase chain reaction), WB (western blot), DMSO (Dimethyl sulfoxide)
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      Biography

      Aiping Qin, PhD, is a gynaecologist subspecializing in reproductive medicine. She is a member of Reproductive Medicine Branch of Chinese Medical Association. Her research interests include fertility protection and abnormal endometrial receptivity, et al. She has published more than 50 articles.