Nav: Home

How fibrosis develops in butterfly syndrome patients

February 06, 2019

PHILADELPHIA - Children with a grave skin disorder known as butterfly syndrome develop severe and chronic blisters. Fibrosis, the thickening and scarring of connective tissues, is a major complication of the disease. Not only can fibrosis lead to club-like appendages where the skin grows over the fingers or toes, but Jefferson's Andrew South, PhD, an associate Professor in the department of Dermatology and Cutaneous Biology, has shown previously that fibrosis in butterfly syndrome patients also leads to an aggressive form of skin cancer that is often fatal. Now, Dr. South and colleagues have pinpointed how fibrosis develops in butterfly syndrome patients. The discovery points to a potential treatment for the debilitating complication.

The scientists suspected a protein called thrombospondin-1 (TSP1) might be involved in fibrosis. In previous research, Dr. South and colleagues discovered skin cells from butterfly syndrome patients have more TSP1 than skin cells from healthy individuals. In the new study, the researchers show TSP1 attaches to a protein that helps to hold layers of the skin together called collagen 7 (C7) in skin cells from healthy individuals. But C7 is missing in butterfly syndrome patients.

"We show for the first time in human cells that TSP1 binds to collagen 7 when it's there," says Dr. South, who published the results online January 23rd in the Journal of Investigative Dermatology. Since children with butterfly syndrome do not have much or any collagen 7, TSP1 instead is able to attach to a different molecule called transforming growth factor-β (TGFβ). TGFβ is a well-known signaling molecule that when activated triggers a cascade of molecular signals that culminate in fibrosis.

"Our data points to that being the major driver of fibrosis in these patients," says Dr. South, who is also a researcher at the Sidney Kimmel Cancer Center - Jefferson Health.

The researchers went on to show a molecule that stops TSP1 from activating TGFβ reduces fibrosis in a tissue engineered model of the symptom. In addition to this potential therapy, the researchers are now sifting through nearly 1,500 FDA-approved molecules to look for other treatments.

"Now that we know one of the major activators of fibrosis is TSP1, we're looking to see whether it's possible to repurpose any of those drugs to treat fibrosis in butterfly syndrome patients," says Dr. South.
-end-
Article reference: Velina S Atanasova, Rebecca J Russell, Timothy G Webster, Qingqing Cao, Pooja Agarwal, Yok Zuan Lim, Suma Krishnan, Ignacia Fuentes, Christina Guttmann-Gruber, John A McGrath, Julio C Salas-Alanis, Andrzej Fertala, Andrew P South, "Thrombospondin-1 is a major activator of TGF-beta signaling in recessive dystrophic epidermolysis bullosa fibroblasts," Journal of Investigative Dermatology, doi: 10.1016/j.jid.2019.01.011, 2019.

Media Contact: Edyta Zielinska, 215-955-7359, edyta.zielinska@jefferson.edu.

Thomas Jefferson University

Related Protein Articles:

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.
Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.
Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.
Protein injections in medicine
One day, medical compounds could be introduced into cells with the help of bacterial toxins.
Discovery of an unusual protein
Scientists from Bremen discover an unusual protein playing a significant role in the Earth's nitrogen cycle.
Protein aggregation: Protein assemblies relevant not only for neurodegenerative disease
Amyloid fibrils play a crucial role in neurodegenerative illnesses. Scientists from Heinrich Heine University Düsseldorf (HHU) and Forschungszentrum Jülich have now been able to use cryo-electron microscopy (cryo-EM) to decode the spatial structure of the fibrils that are formed from PI3K SH3 domains - an important model system for research.
Old protein, new tricks: UMD connects a protein to antibody immunity for the first time
How can a protein be a major contributor in the development of birth defects, and also hold the potential to provide symptom relief from autoimmune diseases like lupus?
Infection-fighting protein also senses protein misfolding in non-infected cells
Researchers at the University of Toronto have uncovered an immune mechanism by which host cells combat bacterial infection, and at the same time found that a protein crucial to that process can sense and respond to misfolded proteins in all mammalian cells.
Quorn protein builds muscle better than milk protein
A study from the University of Exeter has found that mycoprotein, the protein-rich food source that is unique to Quorn products, stimulates post-exercise muscle building to a greater extent than milk protein.
More than a protein factory
Researchers from the Stowers Institute for Medical Research have discovered a new function of ribosomes in human cells that may show the protein-making particle's role in destroying healthy mRNAs, the messages that decode DNA into protein.
More Protein News and Protein Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.