Novel post-translational modifications in fibrosis: The mechanisms and implications

Fibrosis constitutes a pathological phenomenon characterized by excessive deposition of fibrous connective tissue and concomitant reduction of parenchymal cells in tissues and organs. Post-translational modifications (PTMs: chemical modifications of proteins after their synthesis, regulating protein function), including phosphorylation, ubiquitination, and acetylation, encompass biochemical processes occurring following ribosomal protein synthesis, involving covalent conjugation of functional groups to polypeptide chains. Beyond well-characterized modifications, novel PTMs such as propionylation, butyrylation, crotonylation, malonylation, succinylation, glutarylation, and lactoylation are increasingly recognized. While classical and traditional PTMs have received considerable research attention in fibrogenesis, contemporary investigations are elucidating the pathological contributions of novel PTMs to fibrosis progression. This review highlights how novel PTMs contribute to fibrosis progression and discusses their potential as therapeutic targets for anti-fibrotic interventions.