Fibrosis is the body’s way of patching up damage - a bit like fixing a pothole. When skin is cut or a muscle is injured, fibroblast cells rush in to make fibronectin and collagen, which are two major extracellular matrix proteins in tissue. They pull the wound edges together and build a temporary scaffold to let tissue heal.
Once the job is done, the body slowly removes the extra fibres and the tissue softens again. This type of normal wound healing is essential.
However, problems arise when fibroblasts do not stop making fibres. Instead of healing and calming, the tissue becomes thicker, stiffer, and less able to work. This long term, uncontrolled scarring is called pathological fibrosis.
The findings of research from a team led by Dr Seungkuk Ahn, Associate Professor of Cutaneous Biology, UCD School of Medicine and Fellow, UCD Conway Institute helps explain why fibroblasts sometimes switch into this ‘non-stop repair’ mode.
Doğuhan Beyatl, PhD student explains, “This study looked at a protein called fibronectin, which forms tiny fibres in our tissues. In fibrosis, these fibres become very straight and aligned, instead of messy and random like in healthy tissue.
We grew special fibroblast cells on two types of fibronectin fibres – random (healthy) and aligned (fibrotic) fibres. We also used cells that had certain tiny ‘grippers’ called integrins on the cell surface that help cells stick to their surroundings. The two types that were important in sensing fibronectin are αV integrins and α5β1 integrins.”
Describing the key findings, Dr Seungkuk Ahn said, “This study revealed that fibroblasts use α5β1 integrins to sense aligned fibres. When the fibres were aligned, fibroblasts with α5β1 ‘grippers’ stretched out more, formed stronger attachment points and switched on early fibrosis signals.
This early response led to more fibrotic tissue later. After 3 days, fibroblasts with α5β1 ‘grippers’ made thicker, more aligned tissue, more of the main scar tissue proteins and stronger cell–cell and cell–matrix connections.
Interestingly, the fibroblasts with only αV ‘grippers’ did not show strong responses to aligned fibres suggesting that α5β1 is the main driver of fibrosis.”
This study helps scientists understand how fibrosis begins at the very earliest moments—when cells first touch and sense their environment. This could help scientists find new ways to slow down or stop scarring in diseases like skin fibrosis.
Dr Ahn said, “We are really encouraged by these findings. Not only have we taken a leap forward in understanding how fibrosis begins but we believe that α5β1 ‘grippers’ are an interesting potential target for treating fibrosis and curing chronic diseases that feature this process.”