Tenascin C as a Crucial Player in Peritoneal Endometriosis Pathogenesis

New Insights into Endometriosis: Tenascin C’s Role in Early Lesion Formation and Invasion

Key Points

Highlights: 

• Study identifies Tenascin C as a critical factor in the adhesion and invasion of endometriotic lesions in the early stages of the disease.

Importance:

• Study suggests that targeting extracellular matrix components could be an effective strategy for improving treatment outcomes.

What’s done here:

• Uterine tissue fragments were implanted into mice to create lesions, and tissues were collected 3 days later for gene expression and lesion analysis.
• Gene expression in the peritoneum and distant tissues analyzed by PCR to identify factors in adhesion and invasion.
• The role of Tenascin C in endometriosis was studied using knockout mice to compare lesion development in Tenascin C-deficient versus wild-type mice.
• Cell proliferation (Ki67), T cells (CD3), and macrophages were evaluated by immunostaining and fluorescence-activated cell sorting.
• The invasiveness of human endometrial stromal and mesothelial cells was tested after silencing Tenascin C with small interfering RNA.

Key results:

• Knocking down the expression of tenascin C was associated with reduced endometrial lesion weight and number in mice.
• However, nonattached lesions in knockout mice were larger than those in wild-type mice, indicating Tenascin C mportance for attachment.
• Knockout mice lesions showed less cell proliferation (Ki67) and fewer inflammatory cells (CD3), suggesting Tenascin C affects lesion growth and immune response.
• THese lesions also had fewer pro-inflammatory M1 macrophages and more anti-inflammatory M2 macrophages, indicating Tnc influences immune cell behavior.
• Silencing the expression of tenascin C reduced the invasivity of human endometrial stromal cells supporting the role of the protein in the early peritoneal endometriosis.

Lay Summary

Tenascin C, an extracellular matrix protein, may play a key role in the events leading to the development of peritoneal endometriosis, according to a new study published in the journal Fertility & Sterility Science.

To describe elements of the extracellular matrix that may be involved in adhesion and invasion of lesions in the peritoneum in early endometriosis, a team of researchers led by Dr. Fuminori Taniguchi from the Division of Obstetrics and Gynecology, Tottori University Faculty of Medicine in Tottori, Japan conducted a laboratory-based study using tissue samples obtained from five women with ovarian endometrioma as well as a mouse model of endometriosis.

The researchers demonstrated that the expression of tenascin C was significantly higher in the peritoneum surrounding endometrial lesions.

To shed light on the role of tenascin C in endometriosis, the researchers also generated mice in which tenascin C was knocked out. They reported that the weight and number of lesions in these animals were lower than that in wild-type animals, suggesting that the protein may play a role in the attachment of the lesions to the peritoneum. The number of cells that were positive for Ki67 (a protein that is only expressed in diving cells, i.e. a marker of cell proliferation) was reduced in the tenascin C knock-out animals, suggesting that the protein is also involved in cell proliferation. 

The number of inflammatory T cells assessed by CD3 immunostaining were also lower in these animals as was the proportion of M1 pro-inflammatory (or activated) macrophages, while the proportion of anti-inflammatory M2 macrophages was higher. This suggests that tenascin C is also involved in inflammatory pathways.

When they silenced the expression of Tenascin C in human endometrial stromal cells and peritoneal mesothelial cells, the researchers found that the invasivity of human endometrial stromal cells was reduced, once again supporting the role of tenascin C in the formation of peritoneal endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/38092313/