Gossypol May Be Potential Treatment for Lung Fibrosis, Mouse Study Shows

Gossypol May Be Potential Treatment for Lung Fibrosis, Mouse Study Shows
0
(0)

Gossypol — a pharmacological inhibitor of the LDHA enzyme — shows promising results in the prevention and treatment of lung fibrosis, according to a study performed in a mouse model of idiopathic pulmonary fibrosis (IPF). The results point to LDHA as a potential therapeutic target for this disorder.

The study, “Prevention and treatment of bleomycin-induced pulmonary fibrosis with the lactate dehydrogenase inhibitor gossypol,” was published in the journal Plos One.

The differentiation of myofibroblasts — cells that produce collagen and fibronectin proteins, which are involved in scarring (fibrosis) — is crucial for the development and progression of fibrosis. So, targeting myofibroblast differentiation is a potential therapeutic strategy for lung fibrosis.

Previous studies have shown that the lactate dehydrogenase-A (LDHA) enzyme and its product, lactate, are present in high levels in the lung tissue of IPF patients. Lactate was found to induce fibrosis through the activation of transforming growth factor-beta (TGF-β1), which strongly induces myofibroblast differentiation.

The pharmacologic suppression of LDHA with gossypol — a small molecule derived from cottonseed oil —  blocked TGF-β1-induced myofibroblast differentiation and collagen production in cells grown in the lab.

Now, researchers investigated whether gossypol treatment could suppress lung fibrosis in bleomycin-treated mice, a mouse model of human IPF.

Daily administration of gossypol to mice was initiated on the same day as bleomycin, which is a compound that induces lung fibrosis.

Gossypol treatment suppressed bleomycin-induced lung fibrosis, and reduced lung LDHA activity, lactate and collagen accumulation, as well as TGF-β1 activation, compared to untreated mice.

Gossypol also was an effective treatment when started seven days after giving the mice bleomycin, suggesting that LDHA suppression is a potential treatment for lung fibrosis, even when fibrosis is already present.

These findings support previous data pointing to the role of LDHA in TGF-β1-induced myofibroblast differentiation and the development of lung fibrosis.

Also, the block of LDHA activity may be a better strategy “to indirectly reduce TGF-β1 activation, as direct neutralization presents concerns with immune regulation and deficiencies in wound healing,” the researchers wrote.

Gossypol is being studied as a treatment for several types of cancer in clinical trials, but whether it will be an effective treatment in humans remains unclear. The research team believes that improved forms of LDHA inhibitors eventually may be developed and be effective therapeutic strategies in humans.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
×
Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
Latest Posts
  • lung cells
  • protein study
  • lung transplants, outcomes
  • esRAGE protein

How useful was this post?

Click on a star to rate it!

Average rating 0 / 5. Vote count: 0

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?