Fig. 9.

A schematic diagram of the proposed mechanism by which interstitial flow induces MMP-1 expression and SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism. Interstitial flow stimulates the cell, inducing ERK1/2 phosphorylation (mechanotransduction), which enhances AP-1 expression and AP-1 DNA binding activity, leading to an increased expression of MMP-1. Upregulated MMP-1 digests collagen fibers and facilitates cell migration. One of the remaining questions is how cells “sense” interstitial flow and then activate the ERK1/2 pathway.