Cadherin-11 is a novel regulator of extracellular matrix synthesis and tissue mechanics

We discovered that Cadherin-11 (CDH11) regulates collagen and elastin synthesis both affecting the mechanical properties and contractile function of animal tissues. Using a Cdh11 null mouse model, we observed a significant reduction in the mechanical properties of Cdh11−/− as compared to WT (wild type) mouse tissues, such as aorta, bladder and skin. The deterioration of mechanical properties was accompanied by reduced collagen and elastin content in Cdh11−/− mouse tissues as well as cells in culture. Similarly, knocking down CDH11 abolished collagen and elastin synthesis in human cells, and consequently reduced their ability to generate force. Conversely, engagement of CDH11 through homophilic interactions, led to swift activation of the TGF-β and ROCK pathways as evidenced by phosphorylation of downstream effectors. Subsequently, activation of key transcription factors, MRTF-A and MYOCD, led to significant upregulation of collagen and elastin genes. Taken together, our results demonstrate a novel role of adherens junctions in regulating ECM synthesis with implications for many important biological processes including maintenance of tissue integrity, wound healing and tissue regeneration.