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Paracrine Factors Secreted by MSCs Promote Astrocyte Survival Associated With GFAP Downregulation After Ischemic Stroke via p38 MAPK and JNK
Author(s) -
Huang Weiyi,
Lv Bingke,
Zeng Huijun,
Shi Dandan,
Liu Yi,
Chen Fanfan,
Li Feng,
Liu Xinghui,
Zhu Rong,
Yu Lei,
Jiang Xiaodan
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24981
Subject(s) - paracrine signalling , downregulation and upregulation , astrocyte , mapk/erk pathway , p38 mitogen activated protein kinases , glial fibrillary acidic protein , microbiology and biotechnology , mesenchymal stem cell , autocrine signalling , cancer research , biology , signal transduction , endocrinology , cell culture , immunology , biochemistry , central nervous system , genetics , receptor , immunohistochemistry , gene
Astrocytes are critical for ischemic stroke, and understanding their role in mesenchymal stem cell (MSC)‐mediated protection against ischemic injury is important. The paracrine capacity of MSCs has been proposed as the principal mechanism contributing to the protection and repair of brain tissue. In the present study, an in vitro oxygen–glucose deprivation (OGD) model was used to mimic ischemic injury. OGD‐induced astrocytes were reperfused with MSC‐conditioned medium (MSC‐CM) or co‐cultured with MSCs for 24 h to create an environment abundant in paracrine factors. The results indicated that both situations could protect astrocytes from apoptosis, increase cell metabolic activity, and reduce glial fibrillary acidic protein (GFAP) overexpression; however, the effects of co‐culturing with MSCs were more positive. Paracrine factors suppressed the activation of p38 MAPK, JNK, and their downstream targets p53 and STAT1. Inhibition of p38 MAPK, JNK, p53, and STAT1 attenuated astrocyte injury and/or GFAP upregulation. Activation of p38 MAPK and JNK suppressed the beneficial effects of paracrine factors, resulting in decreased survival and GFAP overexpression. These results suggest that paracrine factors inhibit p38 MAPK and JNK, and most likely by regulating their downstream targets, p53 and STAT1, to promote astrocyte survival associated with GFAP downregulation after ischemic stroke in vitro. J. Cell. Physiol. 230: 2461–2475, 2015. © 2015 Wiley Periodicals, Inc.