Thrombomodulin (TM) expressed on vascular endothelial cells plays an important role in activation of the anti-coagulant protein C pathway. TM interacts with multiple ligands and regulates several endothelial cell functions. Here, we found hornerin as a candidate protein interacting to TM on endothelial cell surface by mass spectrometry-based approach. It has reported that hornerin has similar features to filaggrin and implicates in the epidermal barrier function. However, the expression and role of hornerin in endothelial cells is still elusive.
In this study, we confirmed that hornerin protein and mRNA was expressed in endothelium of aorta and cultured endothelial cells by immunofluorescence staining, western blot, and RT-PCR. Lipopolysaccharide (LPS)-mediated sterile inflammation increased serum concentration of hornerin in mice, whereas reduced hornerin from cultured cell. Of note, TM knockdown cells emerged the reduction of hornerin on endothelial cell surface. Furthermore, HRNR knockdown impaired angiogenic tube formation of endothelial cells.
Our findings demonstrated that hornerin is expressed on vascular endothelial cells via the coordinating with TM. Therefore, endothelial hornerin might be an important component in the regulatory machinery of vascular inflammation and angiogenesis.