How a potent anti-fibrotic peptide works and why it reverses scarring in multiple organs

A research team at the Medical University of South Carolina led by Dr.
Feghali-Bostwick, they discovered that the E4 peptide reverses fibrosis or scarring in human and mouse tissue by activating an antifibrotic pathway that is common to all organs and systems
.

The research team's findings are significant because they show that the peptide can effectively reverse fibrosis in multiple organ systems
.
Fibrosis is associated with a variety of diseases, including heart disease, pulmonary fibrosis, liver cirrhosis, and chronic kidney disease

Feghali-Bostwick, the article's senior author, worked at the University of Pittsburgh before joining MUSC and discovered the E4 peptide as a potent anti-fibrotic drug
.
In 2013, he joined MUSC as a visiting professor at SmartState and Kitty Trask Holt, leading scleroderma research

Two of the JCI Understanding article's lead authors, Shailza Sharma, Ph.
D.
, and Watanabe Tomoya, M.
D.
, Ph.
D.
, were members of the Feghali-Bostwick Music Lab, with work done by Tetsuya Nishimoto, Ph.
D.
, a postdoctoral researcher in music who passed away unexpectedly in 2016 After a brief illness, the mechanism was discovered
.

"We discovered this peptide about a decade ago and described its anti-fibrotic activity in different tissues," explains Figali-Bostwick
.
"Our current work explains that the peptide is How it works against fibrosis and what makes it so effective

Fibrosis is the end stage of many diseases, often leading to organ failure

The E4 peptide is derived from a fragment of collagen
.
However, when the parent protein is cleaved, the resulting fragments can have several different roles, including preventing fibrosis

To gain a more complete understanding of how E4 reverses fibrosis, the MUSC team conducted studies to determine how it interacts with other proteins in the body
.
E4 has effects on proteins involved in the urokinase pathway, which is known to inhibit fibrosis

The research team used cells harvested from human lungs for the study
.
Team members also constructed tissue nuclei from fibrotic lungs donated by pulmonary fibrosis patients

E4 was able to reverse fibrosis, even in the end-stage of fibrotic lungs
.
The results, replicated in mice with pulmonary fibrosis, showed that E4 has the same function in a petri dish and in an in vivo system, activating the urokinase pathway in both cases

"It has been shown that when the urokinase pathway is activated, it can effectively reverse fibrosis in different organs," Feghali-Bostwick said
.
"We found a way to activate it with a peptide
.
"

The MUSC study links the E4 peptide to this known anti-fibrotic pathway, providing a possible clinical solution for patients with fibrosis
.

"The intellectual property about the peptide has been licensed and there is a company developing it," Figali-Bostwick said
.
The company, iBio Inc.
, is currently conducting preclinical testing of the peptide and preparing for a Phase 1 safety test.
test
.

"Now that we know how the peptide works, we believe it will benefit fibrosis in different organs," Figali-Bostwick said
.

There were no adverse reactions in the experimental model tested by E4
.

"The peptide is derived from a natural molecule in the human body, so we don't think it will have any side effects," she explained
.

Surprisingly, E4 activates the urokinase pathway by binding to a cell membrane protein called enolase, which is involved in the breakdown of sugars
.
The team will further investigate different binding partners, other mechanisms by which E4 can prevent and reverse fibrosis, and the ideal length of the E4 peptide
.

Figari-Bostwick says it is such meticulous basic research that leads to clinical breakthroughs
.

"It's important to recognize the power of basic research in identifying possible treatments that companies can then develop to provide translational solutions for patients
.
"