Scientists have uncovered key findings about the signalling pathway that causes damaging scar tissue to accumulate in the body.
The hope is that this will raise hopes for future treatments.
The study, published in Nature Communications by a team from the University of Manchester and the University of Connecticut, has revealed how a little-known protein helps keep one of the body’s most potent biological signals tightly controlled.
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, preventing them from functioning properly.
At the centre of the discovery is the signalling molecule transforming growth factor beta (TGFβ), which plays a vital role in the body, helping cells grow, communicate, 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 potent effects, the body normally keeps TGFβ locked away in an inactive state until it is needed.
The team used cryo-electron microscopy, engineered human cell lines and 3D computer simulations to reveal how a key protein regulates TGFβ activity.
Their study revealed for the first time how latent TGFβ-binding protein 1 (LTBP1) helps build and stabilise this storage complex.
They also discovered that LTBP1 does far more than simply hold TGFβ in place, acting as a key regulator that helps keep the molecule safely stored while also influencing how it is released.
The team showed that LTBP1 forms a crucial connection with TGFβ and helps determine how much physical force is required before the signalling molecule can become active.
This mechanical control system ensures that TGFβ is switched on only 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 signalling pathways.
Lead author Professor Clair Baldock of the University of Manchester said: ‘TGFβ is one of the body’s most important signalling molecules, influencing how cells grow, communicate and repair tissue. However, when its activity is not properly controlled, it can contribute to diseases such as fibrosis, in which 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 required to activate it.’
She added: ‘By gaining a clearer understanding of this process, we have uncovered a new layer of biological control that could help researchers develop more precise therapies. We hope our discovery will provide a foundation for future studies aimed at preventing harmful scarring while preserving the body’s normal repair mechanisms.’
