The role of ER stress in PMA-induced megakaryocyte differentiation
| Autor: | Shu-RuYang, 楊淑如 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Platelets are produced from megakaryocyte fragmentation which is crucial for blood coagulation. When hematopoietic stem cells differentiate into megakaryocytes, reactive oxygen species (ROS) and autophagy are essential. On the other hand, endoplasmic reticulum (ER) stress is important for ROS generation and autophagy induction. In addition, ER stress is involved in plasma cell differentiation and T cell development. However, it is still unclear about the role of ER stress in megakaryocyte differentiation. K562 is often used as a cell model for megakaryocyte differentiation study when treated with phorbol ester. In this study, we studied the role of ER stress in PMA-induced K562 differentiation. First, we observed that PMA induced megakaryocyte specific surface marker (CD61, CD42b) expression and DNA polyploidy in K562 cells. Moreover, PMA augmented the production of ROS and increased the expression of autophagy marker, LC3II. Second, we found XBP1 splicing after K562 cells were treated with PMA suggesting ER stress was involved. When IRE1-XBP1 was inhibited, the PMA-induced DNA polyploidy and megakaryocyte surface markers expression were decreased in K562 cells. Furthermore, inhibition of IRE-XBP1 also reduced the production of ROS and the expression of LC3II by PMA. Finally, we observed that XBP1 splicing was decreased by MEK1/2 inhibitors. In summary, our results indicate that the ERK1/2 is an upstream regulator of ER stress and the ER stress affects megakaryocyte differentiation through regulating ROS and autophagy. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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