Skin fibrosis is an often-painful condition wherein the skin thickens and hardens, making it difficult to move. And with no effective treatments currently available, patients are left with few avenues for relief.
In a new study, Yale researchers have started to uncover what happens at the cellular and molecular levels as skin fibrosis progresses, and the findings, they say, yield potential targets for treating fibrotic diseases in the future.
The study was published Jan. 28 in the Journal of Investigative Dermatology.
Previous research has shown that during fibrosis, fat cells in the skin called adipocytes are depleted. Why that happens remains unclear.
“We wanted to understand when this depletion happens and whether it has a function in regulating the fibrotic process,” said Valerie Horsley, professor of molecular, cellular, and developmental biology at Yale School of Medicine and senior author of the study.
To their first question, the researchers found that adipocyte depletion happens quite early in the fibrotic process.
Adipocytes in the skin contain one large liquid droplet of fat molecules (or lipids), which can be released from the cell in response to various biological events. In the two mouse models of skin fibrosis used in the new study, the researchers observed that adipocytes in the area where fibrosis was stimulated lost their lipid droplets as early as five days into fibrosis development.
When the researchers stopped fibrosis stimulation, they saw that the adipocytes refilled with lipids as the skin began to recover.
“That really linked this storage of fat to both the development of fibrosis as well as recovery,” said Horsley.
However, the lipid loss wasn’t driving fibrosis, the researchers found. When they prevented the adipocytes from losing lipids, fibrosis still occurred and was actually more pronounced. The finding suggests lipid loss may be a protective mechanism, said the researchers.
“Adipocytes are somehow sensing that there’s some kind of fibrotic injury and they’re releasing their lipids to try to keep the tissue from becoming fibrotic,” said Horsley. “And we think that once they release all of their lipids, that’s when the skin thickening starts to occur.”
The researchers are now investigating what cells are taking up the lipids released by adipocytes and how those cells are using them. Understanding that, they say, will help identify effective therapeutics for both skin fibrosis and possibly fibrosis that affects other organs, such as the lungs, liver, kidneys, or heart.
Other Yale authors include Elizabeth Caves, Maria Fernanda Forni, Abigail Benvie, Hailey Edelman, Muhammad Hamdan, Ian Odell, and Monique Hinchcliff.