Int J Biol Sci 2019; 15(6):1299-1309. doi:10.7150/ijbs.32677
Novel Role of Heterogeneous Nuclear Ribonucleoprotein E1 in Regulation of Apoptosis and Autophagy by a Triazole Derivative in Vascular Endothelial Cells
1. School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
2. State Key Laboratory of Biobased Material and Green Papermaking, School of Bioengineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China
Meng N, Gong Y, Mu X, Wang YH, Su L, Jiang CS, Zhang H. Novel Role of Heterogeneous Nuclear Ribonucleoprotein E1 in Regulation of Apoptosis and Autophagy by a Triazole Derivative in Vascular Endothelial Cells. Int J Biol Sci 2019; 15(6):1299-1309. doi:10.7150/ijbs.32677. Available from http://www.ijbs.com/v15p1299.htm
Vascular endothelial cell (VEC) apoptosis and autophagy play an important role in the maintenance of vascular homeostasis. However, the association of molecular mechanisms between vascular endothelial cell apoptosis and autophagy has not been clarified. Here, we identified a novel triazole derivative, JL014, which could inhibit human umbilical vein vascular endothelial cell (HUVEC) apoptosis induced by deprivation of serum and fibroblast growth factor 2 and maintain HUVEC survival by promoting autophagy. Importantly, JL014 increased the mRNA and protein level of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) in HUVECs. In addition, knockdown of hnRNP E1 by RNA interference inhibited the effects of JL014 on VEC apoptosis and autophagy. Furthermore, we investigated the effect of JL014 on the expression of HMBOX1, a key VEC apoptosis inhibitor and autophagy inducer by inhibiting mTOR signaling and the level of cleaved caspase-3. Our results demonstrated that JL014 enhanced mRNA transcription and increased protein synthesis of HMBOX1. JL014 also inhibited mTOR signaling and the cleaved caspase-3 level. Mechanistic studies revealed that hnRNP E1 could bind to the promoter and 5'UTR of HMBOX1 and active HMBOX1 expression. Therefore, our results firmly establish hnRNP E1 as a new regulator of VEC apoptosis and autophagy through mediating HMBOX1 expression, and opened the door to a novel therapeutic drug for related vascular diseases.
Keywords: heterogeneous nuclear ribonucleoprotein E1, autophagy, apoptosis, vascular endothelial cell