Heregulin protects mesenchymal stem cells from serum deprivation and hypoxia-induced apoptosis.
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.
Gui
Chun
C
Clinical Research Institute, Affiliated Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310016, P.R. China.
Wang
Jian An
JA
He
Ai Na
AN
Chen
Tie Long
TL
Luo
Rong Hua
RH
Jiang
Jun
J
Hu
Xin Yang
XY
Xie
Xiao Jie
XJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D020890:Neuregulin-1 / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018739:Oncogene Proteins v-erbB / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016895:Culture Media, Serum-Free; D020890:Neuregulin-1; D018739:Oncogene Proteins v-erbB; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D010100:Oxygen