Nav: Home

Connective tissue on the wrong road -- when organs start to scar

February 05, 2019

The increased deposition of connective tissue is a problem in chronic diseases of many organs such as the lungs (idiopathic pulmonary fibrosis), liver (cirrhosis), kidneys (kidney fibrosis), gut (graft versus host disease), and the skin (systemic sclerosis). Up to 40 percent of all deaths in industrial nations are caused by the deposition of connective tissue with subsequent tissue scarring. In spite of this, there are currently very few effective treatments available. Scientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Medicine 3 - Rheumatology and Immunology, headed by Prof. Dr. Georg Schett, have now decrypted a molecular network that controls these processes and could in future provide a new way to treat organ scarring. The results show that the protein PU.1 causes pathological deposition of connective tissue. The scientists have now published their results in the renowned journal Nature.

In connective tissue diseases such as systemic sclerosis, referred to collectively as 'fibrosis', excessive activation of connective tissue cells leads to hardening of the tissue and scarring within the affected organ. In principle, these diseases can affect any organ system and very often lead to disruption of organ function. Connective tissue cells play a key role in normal wound healing in healthy individuals. However, if the activation of connective tissue cells cannot be switched off, fibrotic diseases occur, in which an enormous amount of matrix is deposited in the tissue, leading to scarring and dysfunction of the affected tissue. Until now, scientists did not fully understand why repair processes malfunction in fibrotic diseases.

An international team of scientists led by Dr. Andreas Ramming from the Chair of Internal Medicine III at FAU has now been able to decipher a molecular mechanism responsible for the ongoing activation of connective tissue cells. In experimental studies, the researchers targeted the protein PU.1. In normal wound healing, the formation of PU.1 is inhibited by the body so that at the end of the normal healing process the connective tissue cells can return to a resting state.

'We were able to show that PU.1 is activated in various connective tissue diseases in the skin, lungs, liver and kidneys. PU.1 binds to the DNA in the connective tissue cells and reprogrammes them, resulting in a prolonged deposition of tissue components,' explains Dr. Ramming. PU.1 is not the only factor involved in fibrosis, as factors that are involved in the deposition of scar tissue have already been identified in the past. What has been discovered now, however, is that PU.1 plays a central role in a network of factors controlling this process. 'PU.1 is like the conductor in an orchestra,' explains Ramming, 'if you take it out, the entire concert collapses.' This approach has already been tested using an experimental drug, fuelling the hope that clinical trials on inhibiting PU.1 may soon be able to be launched, aimed at treating fibrosis better.
-end-
The work was supported by Collaborative Research Centre 1181 'Checkpoints for Resolution of Inflammation' of the German Research Foundation.

University of Erlangen-Nuremberg

Related Fibrosis Articles:

A promising target for kidney fibrosis
In a new study published in JCI Insights, investigators report that increasing SMOC2 in the kidney helped initiate and continue the progression of kidney fibrosis, while tamping down SMOC2 prevented it.
Antibody is effective against radiation-induced pulmonary fibrosis
Radiation therapy of the lungs often leads to irreversible connective-tissue changes that cause functional impairments in the pulmonary tissue.
Fighting age-related fibrosis to keep organs young
Their research indicates that an already-FDA-approved drug used by cystic fibrosis patients could shield our organs from fibrosis during acute events, like lung infection or heart attack.
Oddly shaped immune cells cause fibrosis
Scientists at the Immunology Frontier Research Center (IFReC) at Osaka University, Japan, report a new group of monocytes they call SatM.
New study suggests way to slow skin fibrosis in scleroderma
New and ongoing research at Hospital for Special Surgery in New York City has identified a possible mechanism behind the fibrosis that occurs in scleroderma -- a mechanism that may one day lead to a treatment for the disease.
Hormone identified that limits liver fibrosis
Nonalcoholic steatohepatitis has been emerging worldwide and effective treatment, especially for liver fibrosis, is essential for improving the prognosis.
New molecules identified that could help in the fight to prevent cystic fibrosis
New research has identified new molecules that could help in the fight to prevent diseases caused by faulty ion channels, such as cystic fibrosis.
Myocardial fibrosis identified as new therapeutic target
Myocardial fibrosis could be a future therapeutic target after researchers found it correlated with adverse cardiovascular outcomes in patients with obstructive sleep apnoea referred for cardiac magnetic resonance.
Newborn screening for cystic fibrosis
A new study led by a team from the Research Institute of the McGill University Health Centre and Cystic Fibrosis Canada reinforces the benefits of newborn screening for cystic fibrosis (CF) patients.
Three-dimensional imaging of idiopathic pulmonary fibrosis
In this issue of JCI Insight, Mark Jones and colleagues at the University of Southampton in Southampton, UK, used a micro-computed tomography method to create three-dimensional images of fibroblastic foci from patients with idiopathic pulmonary fibrosis.

Related Fibrosis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...