Anastellin impacts on the processing of extracellular matrix and stimulates the release of cytokines from smooth muscle cells

Anastellin, a recombinant protein fragment from the first type III module of fibronectin, mimics a partially-unfolded intermediate with exposed cryptic protein-protein interaction sites implicated in assembly of fibronectin fibrils. Anastellin initiates in vitro fibrillation of fibronectin, yielding “superfibronectin”, a polymer with enhanced cell-adhesive properties. This ability is absent in an anastellin double mutant, L37AY40A. Here we demonstrate that both wild-type and L37AY40A anastellin affects fibronectin processing within the ECM of smooth muscle cells. FN fibrils are diminished in the ECM from cells treated with anastellin, but are partially rescued by supplementation with plasma fibronectin in cell media. Proteomics analysis reveals that anastellin also impacts on the processing of other ECM proteins, with increased collagen and decreased laminin detected in media from cells exposed to wild-type anastellin.