The intracellular form of human MAGP1 elicits a complex and specific transcriptional response

Microfibril-associated glycoprotein-1 (MAGP1) is found associated with microfibrils in the extracellular matrix (ECM). In humans, MAGP1 is expressed as two alternatively spliced isoforms: MAGP1A, the extracellular microfibril-associated form; and MAGP1B, an exclusively intracellular isoform derived from the skipping of exon 3. The biological function of MAGP1B is unknown. We performed gene expression profiling to study the cellular response to MAGP1B using whole-genome genechips. We found that MAGP1B specifically induces the expression of genes linked to cell adhesion, motility, metabolism, gene expression, development and signal transduction. Versican, a gene product involved in the structure and functional regulation of the ECM, showed the highest up-regulation in response to MAGP1B. These studies suggest a dual role for MAGP1, with extracellular MAGP1A involved in ECM function, and intracellular MAGP1B modulating the expression of genes that function in cell adhesion, migration and control of ECM deposition.