Mono (2-ethylhexyl) phthalate (MEHP) triggers the proliferation of hemangioma-derived endothelial cells via YAP signals. (25th September 2019)

• Record Type: Journal Article
• Authors: Ye, Cong; Hu, Yubo; Wang, Junrong; Liu, Dahai; Du, Jianshi
• Is Part Of: Chemico-biological interactions. Volume 311(2019)
• Publication Date: 2019-09-25
• Subjects: MEHP -- Hemangioma -- YAP -- Proliferation -- LATS1/2; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.108773
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Hemangioma (HA) is tumor formed by hyper-proliferation of vascular endothelial cells. However, the potential effects of mono-(2-ethylhexyl) phthalate (MEHP) on the progression of HA are not well illustrated. Our present study revealed that MEHP exposure can significantly increase the in vitro proliferation of hemangioma-derived endothelial cells (HemECs). MEHP treatment can activate yes-associated protein (YAP), a key effector of Hippo pathway, by inhibiting its phosphorylation. The dephosphorylation of YAP induced by MEHP can promote the nuclear accumulation of YAP. Knockdown of YAP or its inhibitor can block MEHP triggered cell proliferation. MEHP can increase the levels of precursor and mature mRNA of YAP in HemECs. As well, MEHP extended the half-life of YAP protein. Mechanistically, MEHP can decrease the phosphorylation of YAP via suppressing the activity of large tumor suppressor kinase 1/2 (LATS1/2) to inhibit it induced degradation of YAP. Further, MEHP increased the expression of interferon regulatory factor 1 (IRF1), which can bind to the promoter of YAP to initiate its transcription. Collectively, we revealed that Hippo-YAP signal is involved in MEHP-induced proliferation of HA cells. Highlights: MEHP triggers the proliferation of HA cells. YAP is involved in MEHP induced cell proliferation. MEHP increases the protein stability of YAP via LATS1/2. MEHP increases the transcription of YAP via IRF1.