Exploring the Impact of NNMT Enzyme on Endometriosis

Alterations in Migration and Invasion Pathways May Drive Enzymatic Overexpression in Endometriosis Development

Key Points

Highlights:

• Modulating nicotinamide N-methyl transferase (NNMT) expression in endometrial stromal cells may promote the shrinkage of endometriotic lesions.

Importance:

• Therapeutic strategies targeting the immunological mechanisms underlying endometriosis should be thoroughly explored to develop effective treatments.

What’s done here?

• A prospective case-control study was conducted to assess NNMT’s role in endometriosis progression.
• Tissue samples from the endometrioma cyst wall and eutopic endometrial tissue of 20 patients undergoing laparoscopic surgery were compared with controls (n=18).
• NNMT expression in ectopic lesions was measured, and its impact on the proliferation, migration, and invasion of endometrial stromal cells was evaluated in vitro and in vivo.
• Additional factors, such as hormone treatment and macrophage co-culture, were tested for their effects on NNMT expression.
• Homologous transplanted models were used to examine NNMT inhibition in vivo.

Key results:

• NNMT overexpression was observed in both eutopic and ectopic tissues of patients with endometriosis.
• Its upregulation enhanced the proliferation, migration, and invasion of endometrial stromal cells.
• NNMT inhibition suppressed endometriosis progression in homologous transplanted models.
• Treatment with 17β-estradiol and macrophage co-culture induced a dose-dependent increase in NNMT expression, promoting cell proliferation, migration, and invasion.
• NNMT knockdown reduced cell proliferation, migration, and invasion.
• NNMT downregulation inhibited cell proliferation by disrupting the ERBB4/PI3K/AKT signaling pathway in endometrial stromal cells.

 Limitations:

• Small sample sizes and monotypic nature of the samples are the limitations of the study, also, the evaluation of the only endometrium and ovarian endometrioma prevents the results from being generalized.

Lay Summary

Endometriosis is driven largely by inflammation and immune dysfunction. Despite extensive research, the optimal treatment for endometriosis remains uncertain. A better understanding of the disease's mechanisms could lead to improved therapies and a better quality of life for affected women.

A recent study by Hou et al., titled "Overexpressed Nicotinamide N‑methyltransferase in Endometrial Stromal Cells Induced by Macrophages and Estradiol Contributes to Cell Proliferation in Endometriosis", published in Cell Death Discovery, investigated the role of nicotinamide N‑methyltransferase (NNMT) in endometriosis.

NNMT expression was evaluated in the endometrioma cyst wall and eutopic endomerium samples of women with endometriosis and compared to the endometrial tissues of women without endometriosis. The potential effect of17β-estradiol hormone treatment and macrophage co-culture on the expression of NNMT in endometrial stromal cells were also examined. 

The researchers found that NNMT was overexpressed in both the cyst wall and eutopic endometrial tissues of women with endometriosis compared to women without the disease. They also observed that hormone treatment (17β-estradiol) and macrophage co-culture led to a dose-dependent increase in NNMT expression, promoting cell proliferation, migration, and invasion. Inhibition of NNMT reduced cell proliferation by interfering with the ERBB4/PI3K/AKT signaling pathway in endometrial stromal cells.

These findings suggest that NNMT plays a significant role in the development of endometriosis and could provide new therapeutic targets for the disease.

Research Source: https://pubmed.ncbi.nlm.nih.gov/39489776/