Gui Chun, Wang Jian An, He Ai Na, Chen Tie Long, Luo Rong Hua, Jiang Jun, Hu Xin Yang, Xie Xiao Jie
Clinical Research Institute, Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310016, P.R. China.
Mol Cell Biochem. 2007 Nov;305(1-2):171-8. doi: 10.1007/s11010-007-9541-3. Epub 2007 Jul 10.
Heregulin can regulate the survival of cardiomyocytes, epithelial cells, neuron, glial cells, and other cell types through binding with the ErbB receptors. The aim of this study is to investigate the effects of heregulin (HRG) on the apoptosis of Bone marrow Mesenchymal stem cells (MSCs). We used the MSCs from adult Sprague-Dawley rats and the model of serum deprivation (SD) and hypoxia-induced apoptosis. The apoptosis was detected by TUNEL method. The apoptosis of MSCs significantly increased 12 h or 18 h after SD and hypoxia, but treatment with HRG significantly decreased the apoptosis induced by SD and hypoxia. Tyrphostin AG1478 (ErbB3/4 inhibitor) or Tyrphostin AG825 (ErbB2 inhibitor) could block this effects of HRG. Akt and ERK were activated by HRG under SD and hypoxia conditions, but HRG had no effects on the activation of JNK and p38. HRG also increased the ratio of Bcl-2/Bax and decreased the activation of caspase3 induced by SD and hypoxia. These results suggested HRG could decrease the apoptosis of MSCs induced by SD and hypoxia through the activation of Akt and ERK, the increase of Bcl-2/Bax ratio and the inhibition of caspase3 activation.
Heregulin可通过与ErbB受体结合来调节心肌细胞、上皮细胞、神经元、神经胶质细胞及其他细胞类型的存活。本研究旨在探讨Heregulin（HRG）对骨髓间充质干细胞（MSCs）凋亡的影响。我们使用了成年Sprague-Dawley大鼠的MSCs以及血清剥夺（SD）和缺氧诱导凋亡模型。通过TUNEL法检测凋亡情况。在SD和缺氧后12小时或18小时，MSCs的凋亡显著增加，但HRG处理显著降低了SD和缺氧诱导的凋亡。酪氨酸磷酸化抑制剂AG1478（ErbB3/4抑制剂）或酪氨酸磷酸化抑制剂AG825（ErbB2抑制剂）可阻断HRG的这种作用。在SD和缺氧条件下，HRG可激活Akt和ERK，但HRG对JNK和p38的激活无影响。HRG还增加了Bcl-2/Bax的比值，并降低了SD和缺氧诱导的caspase3的激活。这些结果表明，HRG可通过激活Akt和ERK、增加Bcl-2/Bax比值以及抑制caspase3激活来减少SD和缺氧诱导的MSCs凋亡。
