Protein acetylation modification in tissue fibrosis: Opportunities and challenges

Protein acetylation (commonly termed lysine acetylation) is a dynamic and ubiquitous post-translational modification (PTM). It is governed by two opposing enzyme families: lysine acetyltransferases (KATs) mediate acetyl group addition to target lysine residues, while lysine deacetylases (KDACs) facilitate their removal. Emerging evidence highlights the crucial regulatory role of protein acetylation in transcriptional regulation, DNA damage response modulation, cytoskeletal remodeling, autophagic flux regulation, and others processes that are involved in fibrotic pathogenesis. Fibrosis is characterized by excessive extracellular matrix (ECM) deposition and represents a pathological wound-healing response to chronic tissue injury. This response leads to organ dysfunction in multiple systems, including the heart, liver, lungs, and kidneys. Based on above findings, this review systematically summarizes the biochemical characteristics of protein acetylation and its role in tissue fibrosis, discusses the interplay between acetylation and other PTMs; finally proposes therapeutic opportunities. In conclusion, this review aim to comprehensively describe protein acetylation's role in tissue fibrosis pathogenesis across organs, highlighting recent advances in targets, profiling techniques, and therapies, while identifying knowledge gaps and future directions.