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    How a potent antifibrotic peptide works and why it could reverse scarring in multiple organs

    Finger clubbing is a classic feature of cystic fibrosis, but it is not found in many patients. Credits: Jerry Nick, MD / Wikipedia

    A research team at the South Carolina Medical College (MUSC), led by Dr. Carol Feger Ribostowick, Journal of Clinical Investment (JCI) Insight The E4 peptide reverses fibrosis or scarring of human and mouse tissues by activating antifibrotic pathways common to all organ systems.

    The team’s findings are important because they suggest that peptides may be effective in reversing. Fibrosis In multiple organ systems. Fibrosis is associated with a variety of illnesses, including heart disease, pulmonary fibrosis, cirrhosis, and chronic kidney disease.

    Feghali-Bostwick, senior author of the article, identified the E4 peptide as a potent antifibrotic agent while working at the University of Pittsburgh, and then MUSC as Chair of the SmartState and Kitty Trask Holt Donations for Scleroderma Research in 2013. I participated in. It reversed fibrosis, but it was not fully understood.

    Two lead authors JCI Insight Dr. Shailza Sharma and Dr. Tomoya Watanabe, members of the MUSC laboratory at Feghali-Bostwick, have completed the work that MUSC postdoc Dr. Tetsuya Nishimoto unexpectedly started. He died in 2016 after a short illness to clarify the mechanism.

    “We identified this peptide about 10 years ago and described its antifibrotic activity in various tissues,” explained Feghali-Bostwick. “Our current research explains how peptides exert anti-fibrotic effects and what makes them very effective.”

    All organ systems share a common pathway to end-stage fibrosis: overproduction and deposition of collagen and similar proteins. Collagen is the connective tissue of the body and provides a physical scaffolding for our organs. However, excess collagen can cause organs to contract, harden, and fail to function properly. Patients with end-stage fibrosis have few treatment options and many require organ transplants.

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

    To better understand how E4 reverses fibrosis, the MUSC team conducted a study to determine how E4 interacts with other proteins in the body. E4 affected proteins involved in the urokinase pathway, which is known to inhibit fibrosis. This pathway works by ultimately activating enzymes that break down excess collagen. This pathway also stops further production of fibrotic collagen.

    The team conducted a study using cells collected from the human lungs. Team members also constructed a tissue core from fibrous lungs donated by patients with pulmonary fibrosis. As healthy lungs are more commonly provided, the core of the tissue was also built from them, after which fibrosis was induced. These tissue cores provide a model more associated with human disease than cells alone.

    E4 was also able to reverse fibrosis in the terminal fibrotic lungs. Results were subsequently reproduced in mice with pulmonary fibrosis, showing that E4 has the same function in the dish and in the biological system, activating the urokinase pathway in both cases.

    “It has already been shown that when activated, the urokinase pathway can effectively reverse fibrosis in various organs,” said Fegari Bostowick. “I found a way to activate it with peptides.”

    The MUSC study associated the E4 peptide with this known antifibrotic pathway to provide a possible clinical solution for patients with fibrosis.

    “Intellectual property around peptides is already licensed and there are companies developing it,” said Fegari Bostowick. The company’s iBio Inc. (Brian, Texas) is currently in preclinical testing of the peptide and is preparing for Phase 1 safety trials.

    “Once we know how peptides work, we are confident that they will be beneficial for fibrosis in various organs,” says Fegari Bostowick.

    No negative side effects were seen in the experimental model in which E4 was tested.

    “I don’t think there are any side effects because the peptides are derived from natural molecules in the body,” 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. Further research will allow the team to investigate various binding partners, additional mechanisms by which E4 can prevent and reverse fibrosis, and the ideal length of the E4 peptide.

    According to Feghali-Bostwick, such in-depth basic research leads to clinical breakthroughs.

    “It is important to understand the power of basic research to identify therapies that companies may develop to provide translation solutions to their patients.”


    A step in fibrosis, a big leap in scleroderma


    For more information:
    Shailza Sharma et al, E4 is involved in uPAR and enolase-1, activates urokinase and exerts an antifibrotic effect. JCI Insight (2021). DOI: 10.1172 / jci.insight.144935

    Quote: How powerful antifibrotic peptides can work to reverse scarring in multiple organs (January 10, 2022) January 10, 2022 https://medicalxpress.com/news/ Obtained from 2022-01-potent-antifibrotic-protein-reverse-scarring.html

    This document is subject to copyright. No part may be reproduced without written permission, except for fair transactions for personal investigation or research purposes. Content is provided for informational purposes only.

    How a potent antifibrotic peptide works and why it could reverse scarring in multiple organs Source link How a potent antifibrotic peptide works and why it could reverse scarring in multiple organs

    The post How a potent antifibrotic peptide works and why it could reverse scarring in multiple organs appeared first on California News Times.

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