Fibrosis is a major driver of organ dysfunction, characterized by excessive collagen accumulation and progressive tissue stiffening, yet effective treatment options remain limited. Understanding how changes in the extracellular matrix (ECM) influence cell behavior is key to identifying new therapeutic strategies.
In a new study from the Layne laboratory, Cheyanne Frosti and co-author Diana Yeritsyan identify a matrix-dependent mechanism by which aortic carboxypeptidase-like protein (ACLP) promotes fibrogenic activation. When bound to collagen, ACLP enhances β1 integrin activation and focal adhesion maturation, leading to downstream RhoA and Rac1 signaling, actin cytoskeletal remodeling, and nuclear accumulation of myocardin-related transcription factor A (MRTFA). These events drive transcriptional programs associated with ECM remodeling and cytoskeletal organization, promoting a pro-fibrotic state.
Importantly, this pathway highlights ACLP as a matrix-derived cue that links ECM composition to integrin-mediated mechanical signaling, providing insight into how physical changes in the ECM contribute to fibrotic disease progression and revealing new potential avenues for therapeutic targets.