The discovery that fibrosis can be driven by a self-sustaining loop opens the door to new strategies for disrupting the process.
Fibrosis, a condition characterized by the accumulation of scar tissue in organs, has long been a challenge in medical science as far a treating it due to the lack of effective treatments to halt or reverse its progression. This scarring, often triggered by chronic inflammation, impairs the normal function of vital organs such as the lungs, liver, heart, and kidneys. Conditions like idiopathic pulmonary fibrosis and fatty liver disease can result. Fibrosis arises from infections, chemical exposure, or severe tissue injury, yet in many cases, the exact cause remains unknown.
Given the elusive nature of the disease, despite years of research, finding effective ways of treating fibrosis are also limited, and because of this, many patients experience severe organ damage and succumb to the disease. What makes fibrosis particularly devastating is the persistent nature of the scarring. Once triggered, the process can become self-sustaining, trapping the body in a cycle of damage that is difficult to stop. Scar tissue lacks the same functionality of healthy tissue, meaning that as it accumulates, organs lose their ability to function normally.
Researchers have been working to better understand the mechanisms that drive fibrosis, with the hope of finding effective targets for future drug therapies. Recently, a team of scientists from the Westmead Institute for Medical Research in Australia, led by Dr. Ziyan Pan, uncovered a molecular feedback loop that sustains fibrosis in multiple organs. By isolating this loop, they have opened new possibilities for targeted treatment.
In their study, the team focused on a key cytokine, transforming growth factor-β (TGFβ), which is known to play a major role in disease development. However, targeting TGFβ directly has proven to be difficult, as it is tied to many other critical functions, making it an unreliable candidate for drug therapy. Instead, Pan and her colleagues searched for alternative ways to disrupt the fibrosis process without affecting other pathways.
Eventually, their research pointed to MERTK, an enzyme found in high levels in fibrotic tissue that may be the key to treating it. In both animal models and human liver biopsy samples from patients with fatty liver disease, elevated MERTK levels were associated with advanced stages of fibrosis. Pan and her team discovered that MERTK not only contributed to the scarring process but also triggered TGFβ expression, creating a positive feedback loop that perpetuated fibrosis. The researchers then tested an experimental drug, UNC569, which inhibits MERTK activity. In mouse models of liver, kidney, and lung fibrosis, the drug not only slowed the progression of fibrosis when applied early on but also reversed existing liver fibrosis in cases where the damage was already well-advanced. This finding is particularly significant – it suggests that MERTK could be a useful target for future antifibrotic therapies.
Although more research is needed to determine whether UNC569 or similar compounds will be safe and effective in humans, the study represents a major step forward in the fight against fibrosis. The discovery that fibrosis can be driven by a self-sustaining loop opens the door to new strategies for disrupting the process. By targeting MERTK, researchers have found a way to stop the cycle of scarring in its tracks, potentially offering relief to millions of patients suffering from fibrotic diseases. As Dr. Pan’s team continues their work, the hope is that their findings will eventually lead to the development of treatments that can halt or even reverse the damage caused by fibrosis across various organs.
Sources:
Inhibition of MERTK reduces organ fibrosis in mouse models of fibrotic disease
Targeting fibrosis: mechanisms and clinical trials | Signal Transduction and Targeted Therapy
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