UK and US scientists have uncovered an important piece of the puzzle on the signaling pathway that causes damaging scar tissue to build up in the body, raising hopes for future treatments.
Published in Nature Communications on 05/08/26, the University of Manchester and University of Connecticut team has revealed how a little-known protein helps keep one of the body's most powerful biological signals under tight control.
Their findings could eventually help researchers develop new ways to tackle conditions linked to fibrosis, a process in which excessive scar tissue forms in organs and prevents them from working properly.
Fibrosis can affect the lungs, liver, kidneys and other organs, and is thought to contribute to millions of deaths worldwide each year.
At the center of the discovery is a signaling molecule called transforming growth factor beta, or TGFβ.
This molecule plays a vital role in the body, helping cells grow, communicate with each other, respond to injury and repair damaged tissue.
However, when there is too much active TGFβ it can trigger the build-up of scar tissue, contributing to a range of serious diseases.
Because of its powerful effects, the body normally keeps TGFβ locked away in an inactive state until it is needed.
They used advanced imaging, called cryo-electron microscopy, engineered human cell lines and 3 dimensional computer simulations to reveal how a key protein regulates TGFβ activity.
The study revealed for the first time how a protein known as latent TGFβ-binding protein 1, or LTBP1, helps build and stabilize this storage complex.
The researchers discovered that LTBP1 does far more than simply hold TGFβ in place.
Instead, it acts as a key regulator, helping to keep the molecule safely stored while also influencing how it is released.
The team showed how LTBP1 forms a crucial connection with TGFβ and helps determine how much physical force is needed before the signaling molecule can become active.
This mechanical control system ensures that TGFβ is only switched on in the right place and at the right time.
The findings provide an important new understanding of how the body regulates one of its most influential signaling pathways.
The scientists believe the work could help guide future efforts to develop treatments that selectively control TGFβ activity in disease.
TGFβ is one of the body's most important signaling molecules because it influences how cells grow, communicate and repair tissue."
Clair Baldock, Lead Author and Professor, The University of Manchester
“But when its activity is not properly controlled, it can contribute to diseases such as fibrosis, where excessive scar tissue damages healthy organs.
“Our study has revealed in unprecedented detail how LTBP1 helps store and regulate TGFβ, and how the structure of this protein complex affects the forces needed to activate it.
“By understanding this process more clearly, we have uncovered a new layer of biological control that could help researchers develop more precise therapies in the future.”
“We hope our discovery will provide a foundation for future studies aimed at preventing harmful scarring while preserving the body's normal repair mechanisms.”
- The Structural basis for the contribution of latent TGFβ binding protein to TGFβ latency and activation is published in Nature Communications on 05/08/26
- The study was funded by the Biotechnology and Biological Sciences Research Council and The Wellcome Trust.
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