Fibulin-5 a Potential Therapeutic Target for the Treatment of Skin Fibrosis

A recent study identified a novel molecule implicated in the development of skin fibrosis, a serious disease characterized by the inflammation and hardening of skin tissue. The study entitled “The matrix protein Fibulin-5 lies at the interface of tissue stiffness and inflammation in fibrosis” was recently published in the journal Nature Communications.

Fibrosis is a widespread disease in which excess of extracellular matrix (ECM) deposition leads to tissue stiffness and swelling, and ultimately to tissue dysfunction. The disease can affect various tissues, such as skin, lungs, heart and liver, and contributes to 30% of all deaths in the world. The basic mechanisms for fibrosis development are not well understood.

Dr. Shyni Varghese, co-senior author of the study, from the University of California, San Diego, said in a press release that in this study researchers identified a new factor that had never been previously associated with fibrosis. He added that this finding contributes to a better understanding of the fibrotic process and may help in the development of new therapeutic strategies probably more efficient than the standard treatments.

In the study, the authors decided to focus on the protein elastin, a small constituent of connective tissues in the body that enables the skin to return to its original form after being stretched. Very little is known about the elastin role in fibrosis. They discovered that the molecule fibulin-5, a protein responsible for the formation of elastin, has a function in the development of skin fibrosis in mice.

The authors detected in a skin fibrosis mouse model significantly higher levels of fibulin-5 when compared with normal mice. Importantly, elevated levels of this molecule were also found in the skin tissues of human patients with skin fibrosis. The team associated high levels of fibulin-5 to increased amounts of elastin that probably induced more skin tissue inflammation and stiffening.

Dr. Colin Jamora, co-senior author of the study, from IFOM-inSTEM Joint Research Laboratory, India, and the University of California, San Diego, said that clinical trials to evaluate the efficiency of potential treatments for several fibrotic diseases until now have been unsuccessful. He added that their work paves the way to new methods to fight this incapacitating condition.

The research team verified that removing fibulin-5 in the skin fibrosis mouse model before the development of the disease prevented the appearance of skin tissue inflammation and stiffening. These findings suggest that fibulin-5 may be a potential therapeutic target for the treatment of skin fibrosis, such as in patients with scleroderma, a chronic autoimmune disease characterized by a hardening and tightening of the skin and connective tissues.

“Manipulating the fibulin-5 levels could be a therapeutic strategy to treat skin fibrosis,” concluded Dr. Varghese.