Researchers discovered how a protein called MTHFD2 helps lung cells make collagen, which causes scarring in a serious lung disease called IPF (Idiopathic Pulmonary Fibrosis). When they blocked this protein in lab tests and animal studies, it reduced scarring and fibrosis. This finding suggests that targeting MTHFD2 could become a new treatment for lung scarring diseases. The study shows how understanding the tiny energy factories in our cells (mitochondria) might help us fight diseases that cause organ damage.

The Quick Take

  • What they studied: How cells make the building blocks needed to create collagen (the protein that causes scarring) in a lung disease called IPF, and whether blocking a specific protein could stop this process
  • Who participated: Human lung cells grown in the laboratory and mice that were given a chemical to mimic lung scarring disease
  • Key finding: When researchers blocked a protein called MTHFD2, lung cells made less collagen and scarring was reduced in mice with lung fibrosis
  • What it means for you: This research suggests a potential new way to treat lung scarring diseases, though it’s still in early stages. If you have IPF or similar conditions, talk to your doctor about clinical trials, as this treatment approach is not yet available for patients

The Research Details

This research combined laboratory experiments with animal testing. First, scientists studied human lung cells in dishes to understand how a disease-causing protein (TGF-β) triggers cells to make collagen. They identified that a protein called MTHFD2 plays a key role in this process by helping cells produce glycine, an amino acid that’s essential for building collagen. Then they tested whether blocking MTHFD2 would reduce scarring in mice that had been given a chemical to cause lung fibrosis, similar to what happens in IPF patients.

Understanding the exact steps that cause lung scarring is important because it helps scientists find new places to intervene with treatments. By identifying MTHFD2 as a critical step in the scarring process, researchers found a potential drug target that could be more effective and have fewer side effects than current treatments.

This study was published in Nature Communications, a highly respected scientific journal. The research combined multiple approaches (cell studies, animal models, and protein blocking) which strengthens the findings. However, because it’s early-stage research, results in animals don’t always translate directly to humans, and more testing is needed before this becomes a treatment option

What the Results Show

When lung cells were exposed to TGF-β (a protein that triggers scarring), they increased production of MTHFD2 and other proteins involved in making glycine. This glycine is then used to build collagen, the main component of scar tissue. When researchers used drugs to block MTHFD2, lung cells made significantly less collagen. In mice with lung scarring, blocking MTHFD2 reduced the amount of scarring and improved lung function. These results suggest that MTHFD2 is essential for the scarring process and could be a target for new treatments.

The study showed that the entire pathway for making glycine (called one-carbon metabolism) is activated when cells receive the scarring signal. This suggests that multiple steps in this pathway might be potential treatment targets. The research also demonstrated that this mechanism appears to be specific to the scarring response, meaning blocking it might not interfere with normal lung cell functions.

Previous research showed that collagen production requires glycine, but scientists didn’t know exactly how cells made this glycine during scarring. This study fills that gap by identifying MTHFD2 as the key enzyme. This builds on earlier work showing that mitochondria (the cell’s energy factories) play important roles in disease, and extends that understanding to lung scarring specifically.

The study was conducted in laboratory cells and mice, not in human patients, so results may not translate directly to people. The sample size of animal studies wasn’t specified in the abstract. Long-term effects of blocking MTHFD2 weren’t fully explored. The research doesn’t yet show whether this approach would work for all types of lung scarring or just IPF. More research is needed to develop safe drugs that can reach lung cells in patients

The Bottom Line

This research is too early-stage to recommend any changes to current IPF treatment. Current standard treatments should continue as prescribed by your doctor. However, this finding may lead to new clinical trials in the coming years. If you have IPF, ask your doctor about participating in clinical trials testing new approaches (moderate confidence - early research stage)

This research is most relevant to people with IPF or other progressive lung scarring diseases, their families, and their doctors. It’s also important for researchers developing new lung disease treatments. People without lung disease don’t need to make changes based on this research

This is basic research, so it will likely take 3-5 years of additional testing before any drug based on these findings could be tested in human patients. If successful, it could take another 5-10 years to become available as a treatment. This is a long timeline, but it’s typical for developing new medicines

Want to Apply This Research?

  • If you have IPF, track your lung function test results (FVC percentage) every 3-6 months as recommended by your doctor, and note any changes in shortness of breath during daily activities using a simple 1-10 scale
  • Set reminders to take current IPF medications exactly as prescribed, and log any new symptoms or changes in breathing. This data will be valuable if you participate in future clinical trials testing MTHFD2-blocking treatments
  • Create a monthly check-in to record breathing difficulty during normal activities, exercise tolerance, and any new symptoms. Share this log with your doctor to track disease progression and discuss whether you might be a candidate for upcoming clinical trials

This research describes early-stage laboratory and animal studies, not human clinical trials. The findings are promising but not yet proven safe or effective in patients. If you have IPF or lung scarring disease, continue following your doctor’s current treatment plan. Do not stop or change any medications based on this research. Always consult with your healthcare provider before making any changes to your treatment. This information is for educational purposes and should not be considered medical advice. Clinical trials testing MTHFD2-blocking drugs in humans have not yet begun.