Galectin-3 promotes fibrosis in ovarian endometriosis

PeerJ. 2024 Feb 14:12:e16922. doi: 10.7717/peerj.16922. eCollection 2024.

Abstract

Objective: This study aimed to investigate the potential role of galectin-3 (Gal-3) in the pathogenesis of fibrotic alterations in ovarian endometriosis (OVE).

Methods: In this study, we collected the ectopic endometrial tissues and eutopic endometrial tissues from 31 OVE patients treated by laparoscopy, and the eutopic endometrial tissues from 23 non-OVE patients with leiomyoma or other benign diseases were used as control. Hematoxylin and eosin (H&E) and Masson's trichrome staining were utilized for histopathological assessment. The primary normal endometrial stromal cells (NESC), ectopic endometrial stromal cells (ECSC), and eutopic endometrial stromal cells (EUSC) were isolated. Gal-3 overexpression plasmids (Gal-OE) and short hairpin RNA targeting Gal-3 (Gal-3-shRNA) were transfected into the immortalized human endometriotic cell line 12Z, respectively. RT-qPCR, Western blot analysis, and immunohistochemistry were used to detect the mRNA and protein expression levels of Gal-3, type I collagen (COL-1), connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), respectively.

Results: H&E and Masson staining showed that ovarian ectopic endometrium exhibited glandular hyperplasia, high columnar glandular epithelium, apical plasma secretion, more subnuclear vacuoles, and obvious fibrosis, compared with normal endometrium. The mRNA and protein levels of Gal-3 , CTGF, α-SMA, and COL-1 were all upregulated in the ectopic endometrial tissues of OVE patients compared to the eutopic endometrial tissues from OVE patients and non-OVE patients. Moreover, ECSC expressed higher levels of Gal-3, CTGF, α-SMA, and COL-1 than EUSC and NESC. Follow-up investigations demonstrated that the Gal-3 overexpression substantially increased fibrosis-related markers including CTGF, α-SMA, and COL-1 within the 12Z cell line. Conversely, Gal-3 knockdown showed the opposite effects.

Conclusion: Gal-3 promotes fibrosis in OVE, positioning it as a prospective therapeutic target for mitigating fibrosis in endometriosis.

Keywords: 12Z cells; Fibrosis; Galectin-3; Ovarian endometriosis.

MeSH terms

  • Collagen / metabolism
  • Endometriosis* / genetics
  • Female
  • Fibrosis
  • Galectin 3* / genetics
  • Humans
  • RNA, Messenger / metabolism
  • Stromal Cells / metabolism

Substances

  • Collagen
  • Galectin 3
  • RNA, Messenger
  • LGALS3 protein, human

Grants and funding

This study was supported by the Key Special Project of the “Ministry of Science and Technology on the Prevention and Control of Reproductive Health and Major Birth Defects” of the China (No. 2017YFC1001204). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.