Researchers Identify Gene That Can Inhibit the Progression of Pulmonary Fibrosis

Researchers Identify Gene That Can Inhibit the Progression of Pulmonary Fibrosis

A gene called FOXF1 can inhibit the progression of idiopathic pulmonary fibrosis (IPF), according to scientists at the Cincinnati Children’s Hospital Medical Center.

They reported that IPF patients’ lungs, as well as the lungs of mouse models of IPF, lack the gene in cells called myofibroblasts that play a key role in tissue scarring, or fibrosis. The finding in patients involved experiments with lung tissue in a lab.

The team also found a connection between the loss of the FOXF1 gene and overactivity in another gene — FOXM1 — that drives lung tissue inflammation and scarring.

They titled their study in the journal Cell Reports “FOXF1 inhibits pulmonary fibrosis by preventing CDH2-CDH11 cadherin switch in myofibroblasts.

The causes of IPF are still poorly understood, but genetic predisposition to disease, smoking and other environmental factors play a role.

A process that appears to be involved is epigenetics, or external modifications to DNA that turn genes on or off without changing the DNA sequence. One way that epigenetics can control gene activity is by using a transcription factor — a regulator gene that tells other genes what to do. This includes telling them what biological processes to activate or inhibit and what proteins to make.

In a study funded by the National Institutes of Health, the Cincinnati researchers investigated the transcription factor FOXF1‘s control over two genes called cadherins —  CDH2 and CDH11.

They discovered below-normal FOXF1 activity in the myofibroblasts of lungs with IPF —both in patients’ tissue in a lab and in mouse models of the disease. Another finding was that the loss of FOXF1 led to increased collagen production and the migration of myofibroblasts to other parts of the lung— two situations involved in scar tissue formation.

The team also discovered that FOXF1 triggers CDH2 activity but inhibits CDH11, a combination that prevents IPF from progressing. In addition, they learned that FOXF1 regulates the activity of the FOXM1 gene. When FOXF1 is inactive, FOXM1 is over-active, causing lung fibrosis and inflammation, they said.

“The exact cause of IPF is unknown and effective treatments are needed,” Tanya Kalin, MD, PhD, the lead investigator of the research, said in a press release. “This study identifies a novel anti-fibrotic drug target that inhibits pulmonary fibrosis” in lab and animal models, she said. “We are developing different therapeutic approaches and conducting” preclinical-trial tests “to increase FOXF1 expression in the cells of lung connective tissues,” she added.

The researchers think they will need two to three more years of laboratory and animal studies before deciding whether they can test a potential treatment in clinical trials.

They are now working on ways to increase FOXF1 levels in IPF. One approach is testing a small molecule that could stabilize FOXF1 and inhibit myofibroblasts in IPF.

The team will also try using nanoparticles to deliver FOXF1 genes to patients’ lung cells.

 

 

6 comments

  1. Denny Watkins says:

    The article’s title is “Researchers Identify Gene That Can Inhibit the Progression of Pulmonary Fibrosis” yet the article speaks to only Idiopathic Pulmonary Fibrosis (IPF). I thought there were differences between PF & IPF. Does research and the findings in these areas (PF & IPF) include both, independent of each other or do they intersect?

    • Diogo Pinto says:

      Hi Denny, thank you for your comment. The article refers specifically to Idiopathic Pulmonary Fibrosis, a specific type of Pulmonary Fibrosis. Sorry for the misunderstood.

  2. Pat Hamilton says:

    I have been on ofev and stopped taking due to neausa and the espriett I get severe diarrhea so I would love suggestions on dealing with these side effects.

    • Cynthia Scott says:

      just a thought – did you reduce the ofev dosage and still get nausea? I had to cut back on my dosage of Espriet because of the same side effect but am doing fine on 2 pills 3X a day

Leave a Comment

Your email address will not be published. Required fields are marked *