Extracellular S100A4 as a key player in fibrotic diseases

Abstract

Fibrosis is characterized by fibroblast activation, extracellular matrix (ECM) accumulation and infiltration of inflammatory cells that sometimes leads to irreversible organ dysfunction. Considerable evidence now indicates that inflammation plays a critical role in the initiation and progression of organ fibrosis. S100A4 protein, a ubiquitous member of the S100 family, has recently been discovered as a potential factor implicated in fibrotic diseases. S100A4 protein is released at inflammatory site and has a certain biological function to promote cell motility, invasion, ECM remodelling, autophagy and angiogenesis. In addition, extracellular S100A4 is also a potential causation of inflammatory processes and induces the release of cytokines and growth factors under different pathological conditions. Elevated S100A4 level in patients’ serum closely correlates with disease activity in several fibrotic diseases and serves as a useful biomarker for diagnosis and monitoring disease progression. Analyses of knockout mouse models have identified a functional role of extracellular S100A4 protein in fibrotic diseases, suggesting that suppressing its expression, release or function might be a promising therapeutic strategy. This review will focus on the role of extracellular S100A4 as a key regulator of pro‐inflammatory signalling pathways and its relative biological processes involved in the pathogenesis of fibrosis.