caa a22 4500 606233687 CHVBK 20210128101233.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2361-y doi (NATIONALLICENCE)springer-10.1007/s11010-015-2361-y Improved survival of mesenchymal stem cells by macrophage migration inhibitory factor [Elektronische Daten] [Wenzheng Xia, Congying Xie, Miaomiao Jiang, Meng Hou] Macrophage migration inhibitory factor (MIF) is a critical inflammatory cytokine that was recently associated with progenitor cell survival and potently inhibits apoptosis. We examined the protective effect of MIF on hypoxia/serum deprivation (SD)-induced apoptosis of mesenchymal stem cells (MSCs), as well as the possible mechanisms. MSCs were obtained from rat bone marrow and cultured in vitro. Apoptosis was induced by culturing MSCs under hypoxia/SD conditions for up to 24h and assessed by flow cytometry. Expression levels of c-Met, Akt, and FOXO3a were detected by Western blotting. CD74 expression was detected by qRT-PCR, Western blot, and immunofluorescence. Oxidative stress under hypoxia/SD was examined by detection of reactive oxygen species (ROS) and activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Hypoxia/SD-induced apoptosis was significantly attenuated by recombinant rat MIF in a concentration-dependent manner. MIF induced CD74-asssociated c-Met activation, which was blocked by knocking down CD74 expression using siRNA. MIF also induced Akt and associated FOXO3a phosphorylation, and this effect was abolished by knocking down either CD74 or Akt. In addition, MIF decreased oxidative stress in MSCs, as shown by decreased ROS and MDA, and increased the activity of SOD. Knockdown of CD74, Akt, or FOXO3a largely attenuated the anti-apoptotic effect of MIF and its ability to protect against oxidative stress. MIF protected MSCs from hypoxia/SD-induced apoptosis by interacting with CD74 to stimulate c-Met, leading to downstream PI3K/Akt-FOXO3a signaling and decreased oxidative stress. The Author(s), 2015 Mesenchymal stem cells nationallicence Hypoxia/serum deprivation-induced apoptosis nationallicence MIF nationallicence PI3K/Akt-FOXO3a signaling pathways nationallicence Oxidative stress nationallicence Xia Wenzheng Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China aut Xie Congying Department of Radiation Oncology, First Affiliated Hospital, Wenzhou Medical University, 325000, Wenzhou, China aut Jiang Miaomiao Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China aut Hou Meng Department of Radiation Oncology, First Affiliated Hospital, Wenzhou Medical University, 325000, Wenzhou, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 11-24 0300-8177 404:1-2<11 2015 404 11010 https://doi.org/10.1007/s11010-015-2361-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2361-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xia Wenzheng Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China aut NATIONALLICENCE 700 1- Xie Congying Department of Radiation Oncology, First Affiliated Hospital, Wenzhou Medical University, 325000, Wenzhou, China aut NATIONALLICENCE 700 1- Jiang Miaomiao Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China aut NATIONALLICENCE 700 1- Hou Meng Department of Radiation Oncology, First Affiliated Hospital, Wenzhou Medical University, 325000, Wenzhou, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 11-24 0300-8177 404:1-2<11 2015 404 11010