Researchers here suggest that PU.1 is a master regulator of fibrosis, and thus inhibition could be an effective treatment for the various fibrotic diseases that presently lack good options for patients. Fibrosis is a dsyregulation of the normal processes of tissue maintenance, in which scar-like deposits of collagen are formed, disrupting tissue structure and function. When this progresses far enough, it is ultimately fatal: consider the fibrotic diseases of heart, lungs, and kidney, for example. There is evidence for the presence of senescent cells to contribute to fibrotic diseases. Given this new information about PU.1 it, it will be interesting to see if the mechanisms by which scarring forms can be traced back to specific signaling on the part of senescent cells, and thus further reinforce senolytics as a therapy for fibrosis.
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.
Researchers 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 reprograms them, resulting in a prolonged deposition of tissue components."
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. 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 better treating fibrosis.