Gene expression profiling of Tsp1 deficient rat aortic smooth muscle cells with mechanical stretch

The extracellular matrix (ECM) initiates mechanical cues and transduces intracellular signaling through matrix-cell interactions. The nature of cues and how they coordinate with a mechanical microenvironment are not fully understood. We identified the matricellular protein,thrombospondin-1 (Tsp1, also called Thbs1),as a mediator of matrix mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to cyclic stretch. Thbs1-mediatedYAP activation depends on the small GTPase Rap2 and Hippo pathway, and is not influenced by altered actin fibers. Hence, to gain insight into the molecular mechanisms underlying the Tsp1-mediated matrix mechanotransduction, we performed a comprehensive analysis of gene expression changes in Tsp1deficiant SMCs with mechanical stretch using RNA sequencing (RNA-Seq).