Many chronic diseases occurring in organs are caused due to increased deposition of connective tissue followed by scarring. Now, researchers have uncoded a molecular network that is responsible for these processes and could also lead to new therapies in the future for organ scarring. According to the study, a protein known as PU.1 causes pathological deposition of connective tissue.
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 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.
'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 reprograms 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.