Egr-1: A Target for Scleroderma Therapy PDF Print E-mail
Monday, 26 April 2010 15:10
Two separate research groups funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered that the molecule EGR-1 (early growth response 1), which regulates gene expression, plays a central role in the development of fibrosis, a condition in which organ-supporting tissue becomes thick, hard, and rigid, hindering normal tissue and organ function. Controlling EGR-1, say the scientists, could be a potential therapy for such disorders as Scleroderma and pulmonary fibrosis. Their findings have been reported in the American Journal of Pathology.

Fibrosis is a disorder of the extracellular matrix, the mesh of proteins like collagen that makes up the body’s connective tissue. It is a factor in scleroderma, among other diseases, and can affect many of the body’s organs, including the lungs, liver, and skin. Its consequences can be devastating, even leading to death. Recent research has shown that cells in fibrotic tissue receive the wrong molecular signals, causing too many extracellular proteins to be made. One possible way to approach the fibrosis problem, scientists say, might be to try to interrupt such signals at critical points in the cellular pathways that they travel.

The two research groups, headed by Carol Feghali-Bostwick, Ph.D., at the University of Pittsburgh School of Medicine and John Varga, M.D ., at Northwestern University’s Feinberg School of Medicine, took separate approaches in discovering the importance of EGR-1. The University of Pittsburgh group induced fibrosis in mouse and human fibroblasts (cells that make up the extracellular matrix) by utilizing a signaling protein called IGFBP-5 (insulin-like growth factor binding protein 5). The Northwestern team administered the antibiotic bleomycin to induce scleroderma in mice. Both research teams found that the experimentally produced fibrosis was associated with abnormally elevated EGR-1 activity.

Furthermore, when they produced fibrosis in cells or in mice lacking EGR-1, the amounts of fibrosis were dramatically reduced. In further support of the findings, the Pittsburgh group found that EGR-1 levels were higher in lung tissues and fibroblasts of people with pulmonary fibrosis compared to controls. EGR-1, concluded the scientists, appears to be essential for the development of fibrosis, making it a potential target for therapy. The two studies also showed that independent signaling pathways, such as those for IGFBP-5 and bleomycin, both converge on EGR-1 to create fibrosis.

Fibrosis is a common disorder and a serious complication of many diseases. It is still considered hard to treat, with no currently approved therapies. Because the understanding of fibrosis is a major unmet medical need, any fresh insights into the disease process might open the door for novel therapies.

Source: 7th Space
 
More articles :

» Actelion Fibrosis Drug Doesn't Meet Key Endpoint

Actelion Ltd today announced the initial results of BUILD-3, a clinical study evaluating the safety and efficacy of Bosentan in patients suffering from idiopathic pulmonary fibrosis. While there was a consistent trend in favour of Bosentan, the...

» Thoracic Outlet Syndrome Secondary to Localized Scleroderma Treated With Botulinum Toxin Injection

Localized scleroderma is characterized by thickening of the skin and subcutaneous tissue. Depending on clinical and pathologic findings, localized scleroderma is classified into different subtypes: plaque morphea, generalized morphea, bullous...

» Dysexecutive Syndrome A Specific Pattern of Cognitive Impairment in Systemic Sclerosis

Systemic sclerosis (SSc), also called scleroderma, is a connective-tissue disorder characterized by obliterative microvascular lesions and diffuse interstitial fibrosis. SSc damages the small and medium-sized vessels serving the skin, joints...

» The Role of Intravenous Immunoglobulin Preparations in the Treatment of Systemic Sclerosis

Marta Baleva and Krasimir NikolovReceived 12 June 2011; Revised 28 August 2011; Accepted 28 August 2011Scleroderma is progressive autoimmune disease associated with severe disability. The major underlying pathological process in Scleroderma is...

» The Secrets of An Ancient Chinese Remedy, Revealed

For roughly two thousand years, Chinese herbalists have treated malaria using a root extract, commonly known as Chang Shan, from a type of that grows in Tibet and Nepal. Recent studies suggest that , a compound derived from the extract’s bioactive...

» Actelion Pharmaceuticals announces availability of PAH Mobile Reference Guide

Actelion Pharmaceuticals US, Inc. is announcing the availability of the Pulmonary Arterial Hypertension (PAH) Mobile Reference Guide, the first multimedia smart phone application that provides information on PAH disease, pathology, diagnosis, and...

Comments  

 
+1 #2 Nia 2012-09-16 23:51
i hve sd, very grateful for this research. wouldnt be suprised if there's a vaccine for autoimmune doseases in the not too distant future.
Quote | Report to administrator
 
 
+1 #1 Nia 2012-09-16 23:50
Quote:
exciting!
didnt know SD could be induced with an antibiotic...
Quote | Report to administrator
 

Add comment

Do feel free to leave your comments, as they would add value and knowledge to the community. However, please refrain from making any disparaging, uninformed, or unrelated comments. Thanks :)

Security code
Refresh