Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Blood and Cancer Biology Laboratory, Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Genes Cells. 2024 Oct;29(10):889-901. doi: 10.1111/gtc.13151. Epub 2024 Aug 13.
Endoplasmic reticulum stress triggers the unfolded protein response (UPR) to promote cell survival or apoptosis. Transient endoplasmic reticulum stress activation has been reported to trigger megakaryocyte production, and UPR activation has been reported as a feature of megakaryocytic cancers. However, the role of UPR signaling in megakaryocyte biology is not fully understood. We studied the involvement of UPR in human megakaryocytic differentiation using PMA (phorbol 12-myristate 13-acetate)-induced maturation of megakaryoblastic cell lines and thrombopoietin-induced differentiation of human peripheral blood-derived progenitors. Our results demonstrate that an adaptive UPR is a feature of megakaryocytic differentiation and that this response is not associated with ER stress-induced apoptosis. Differentiation did not alter the response to the canonical endoplasmic reticulum stressors DTT or thapsigargin. However, thapsigargin, but not DTT, inhibited differentiation, consistent with the involvement of Ca signaling in megakaryocyte differentiation.
内质网应激触发未折叠蛋白反应（UPR）以促进细胞存活或凋亡。据报道，短暂的内质网应激激活可触发巨核细胞生成，UPR 激活被认为是巨核细胞癌的特征。然而，UPR 信号在巨核细胞生物学中的作用尚不完全清楚。我们使用 PMA（佛波醇 12-肉豆蔻酸 13-醋酸酯）诱导巨核细胞前体细胞系成熟和血小板生成素诱导人外周血祖细胞分化来研究 UPR 在人类巨核细胞分化中的作用。我们的结果表明，适应性 UPR 是巨核细胞分化的一个特征，并且这种反应与内质网应激诱导的细胞凋亡无关。分化并没有改变对经典内质网应激剂 DTT 或 thapsigargin 的反应。然而，thapsigargin 而不是 DTT 抑制了分化，这与 Ca 信号在巨核细胞分化中的参与一致。
