A Proteomics Resource Investigating Fibrosis: Proof-of-Concept for Identifying Novel Drug Candidates

Fibrosis is characterised by inappropriate wound healing and the buildup of excessive fibrous connective tissue, in particular within the extracellular matrix (ECM). This can occur in multiple organs, ultimately leading to organ failure. Despite the high burden of fibrosis, treatment options only delay disease progression. Therefore, leveraging publicly available proteomics data, we investigated whether common fibrotic proteins and pathways in different organs could be found, to define potential core changes related to fibrosis. We identified 124 significantly differentially expressed proteins in heart fibrosis, four in early-versus-mild liver fibrosis, 135 in mild-versus-severe liver fibrosis and 160 in early-versus-severe liver fibrosis. Functional annotation of each of these groups of proteins demonstrated a consistent upregulation of ECM proteins and a consistent downregulation of proteins associated with mitochondrial activity. Using these data for drug repurposing, 26 compounds were proposed for further investigation, with 20 of them having demonstrated a promising anti-fibrotic effect. A core set of 18 proteins were shared between heart and liver fibrosis, and are associated with increased ECM deposition and fibroblast activation. This approach can be generalised for other pathologies, improving the knowledge on the affected molecular pathways, and based on this, identifying potential drug candidates/compounds.