Study Identifies Potential New Theraputic Target in Endometriosis

Lactate could play a role in the development and progression of endometriosis and targeting the process of lactylation could be a potential new therapeutic avenue in endometriosis.

Key Points

Highlights: 

• Histone lactylation may play an important role in the progression of endometriosis.

Importance:

This finding can help researchers develop new treatments that can halt the development or progression of endometriosis.

What’s done here:

• Researchers analyzed the effect of lactate on histone proteins in endometriosis
• They also analyzed the effect of lactate treatment in endometriosis.

Key results:

• Lactate increased the lactylation of the histone H3 lysine in ectopic endometrial tissues and ectopic endometrial stromal cells.
• Lactate treatment drove cell proliferation, migration, and invasion in endometriosis.
• Lactate exerted its activity through the HMGB1 gene.

Limitations:

• More research is needed to confirm the role of lactate in endometriosis.

Lay Summary

Lactate could drive the progression of endometriosis by upregulating the expression of a gene called HMGB1, according to a new study published in the Journal of Biomedical Research. This finding identifies novel targets for the prevention and treatment of endometriosis.

The possible role of lactylation in endometriosis is not yet known. However, it is known that the process is involved in the proliferation and metastasis of certain types of cancer.

In the present study, a team of researchers from China analyzed the possible role of lactate and lactylation in endometriosis. They reported that lactate and lactate dehydrogenase A increased the lactylation of the histone H3 lysine in ectopic endometrial tissues and ectopic endometrial stromal cells more so than in normal endometrial tissues and endometrial stromal cells.

Moreover, lactate drove cell proliferation, migration, and invasion in endometriosis.  The researchers also showed that lactate exerted its activity by driving the expression of HMGB1. Knocking down the HMGB1 gene significantly reduced the proliferation, migration, and invasion of cells treated with lactate.

“Lactate could induce histone lactylation to promote endometriosis progression by upregulating the expression of HMGB1,” the researchers concluded.

Lactate is a byproduct of glycolysis, which is the process of glucose being broken down to produce energy. Lactylation is a process that modifies the structure of chromosomes, thereby facilitating the expression of certain genes.

HMGB1 or high-mobility group box 1 is a protein that is important for the replication and differentiation of cells and the transcription of certain genes.

Research Source: https://pubmed.ncbi.nlm.nih.gov/37945340/