Bleomycin induces endothelial mesenchymal transition through activation of mTORpathway: a possible mechanism contributing to the sclerotherapy of venous malformations

• DOI: 10.1111/bph.12355
• Publication Date: 2013-08-29T02:12:55Z
• Authors: Wei Zhang; Gang Chen; Jian‐Gang Ren; Yi‐Fang Zhao
• Keywords: Sirolimus; 0303 health sciences; TOR Serine-Threonine Kinases; Sclerosing Solutions; 3. Good health; Veins; Bleomycin; 03 medical and health sciences; Cell Movement; Cell Transdifferentiation; Sclerotherapy; Human Umbilical Vein Endothelial Cells; Humans; Snail Family Transcription Factors; Vascular Diseases; Proto-Oncogene Proteins c-akt; Transcription Factors

Bleomycin (BLM), one of the most common sclerosants, is often used to treat venous malformations (VMs). The present study was designed investigate whether endothelial mesenchymal transition (EndoMT) contributes therapeutic effects BLM.Endothelial and markers HUVECs were measured by immunofluorescence, real-time quantitative PCR Western blot analysis. Cell migration tube formation assays performed evaluate cell function. Slug small-interfering RNA specific inhibitors [Z-VAD-FMK for pan caspases, rapamycin mammalian target (mTOR)] mechanism.Long term (48 h or longer) treatment with BLM (0.1 mU·mL(-1) ) induced EndoMT in HUVECs, as manifested a reduction expression vascular endothelial-cadherin an up-regulation α-smooth muscle actin fibroblast protein-1, well activation transcription factor Slug. size protein content transformed cells increased. also enhanced but diminished their formation. By employing rapamycin, we demonstrated that mTOR pathway involved BLM-induced HUVECs.Our results show Slug-dependent process on and, more importantly, indicate potential role this sclerotherapy VMs.