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Transforming Growth Factor-β Receptor Internalization via Caveolae Is Regulated by Tubulin-β2 and Tubulin-β3 During Endothelial-Mesenchymal Transition

Transforming Growth Factor-β Receptor Internalization via Caveolae Is Regulated by Tubulin-β2 and Tubulin-β3 During Endothelial-Mesenchymal Transition

Katarzyna Sobierajska, Marta E Wawro, Wojciech M Ciszewski, Jolanta Niewiarowska

Am J Pathol. 2019 Dec;189(12):2531-2546.

PMID: 31539520

Abstract:

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 and tubulin-β3 in microtubules enhances sensitivity to TGF-β1 stimulation in human microvascular endothelial cells. We observed that the microtubules enriched in glycosylated tubulin-β2 and tubulin-β3 were necessary for caveolae-dependent TGF-β receptor internalization. Post-translational 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248690	Transforming Growth Factor-β3 human			Price

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