A groundbreaking study published in the journal Gut has identified extracellular matrix protein 1 (ECM1) as a critical “gatekeeper” in preventing liver fibrosis, a severe consequence of chronic liver disease. The discovery provides a promising foundation for the development of novel treatments for this currently untreatable condition.
Liver fibrosis, which affects approximately 500,000 people in Germany, results from chronic liver damage caused by factors such as excessive alcohol consumption, hepatitis infections, and fatty liver disease. It is marked by the replacement of healthy liver tissue with connective tissue, leading to scarring and progressive loss of liver function.
As reported by medicalxpress, the study, led by doctoral researcher Frederik Link under the supervision of Dr. Sai Wang, sheds light on how ECM1 suppresses the activation of the signaling molecule transforming growth factor-β (TGF-β), a key driver of fibrosis. In its biologically active form, TGF-β triggers hepatic stellate cells (HSCs) to transform into myofibroblasts, which overproduce connective tissue. By keeping TGF-β in its inactive state, ECM1 prevents this fibrotic process, maintaining liver health.
The researchers further identified mediators involved in the activation of TGF-β, including thrombospondin-1 (TSP-1), ADAMTS protease 1 (ADAMTS1), and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). Their experiments revealed that ECM1 interacts with these mediators through specific amino acid sequences, effectively blocking the activation of latent TGF-β (LTGF-β). These findings were confirmed in mouse models and supported by data from liver tissue samples of patients with chronic liver disease, where ECM1 levels inversely correlated with LTGF-β activation and the expression of the identified mediators.
This breakthrough builds on earlier research from 2019, when the Mannheim team, in collaboration with scientists from Shanghai, first established ECM1’s role in liver health. The latest study underscores ECM1’s protective function and highlights its potential as a therapeutic target for liver fibrosis.
“Liver fibrosis remains a significant medical challenge, with no effective treatments available. Our findings offer new insights into the molecular mechanisms at play and pave the way for potential therapies,” said Dr. Sai Wang.
The team has proposed several approaches to leverage ECM1’s protective properties for therapeutic applications, which are now the focus of ongoing research. These developments mark a significant step forward in the fight against liver fibrosis and chronic liver disease.