Transforming growth factor-β receptor internationalization via caveolae is regulated by tubulin-β2 and tubulin-β3 during endothelial-mesenchymal transition.

Fibrotic disorders, which are caused by long-term inflammation, are observed in numerous organs. These disorders are regulated mainly through transforming growth factor (TGF)-β family proteins by a fundamental cellular mechanism, known as the endothelial-mesenchymal transition. Therefore, there is a pressing need to identify the mechanisms and potential therapeutic targets that enable the inhibition of endothelial transdifferentiation. This study is the first to demonstrate that glycosylation of tubulin-β2 (TUBB2) and tubulin-β3 (TUBB3) in microtubules enhances sensitivity to TGF-β1 stimulation in human microvascular endothelial cells. We observed that the microtubules enriched in glycosylated TUBB2 and TUBB3 were necessary for caveolae-dependent TGF-β receptor internalization. Posttranslational modulation is critical for the generation of myofibroblasts through endothelial-mesenchymal transition during fibrosis development. We suggest that microtubule glycosylation may become the target of new effective therapies for patients with recognized fibrotic diseases.