Lipopolysaccharides protect Mesenchymal Stem Cell against Cardiac
Ischemia-reperfusion Injury by HMGB1/STAT3 signaling
Myocardial ischemia-reperfusion (I/R) is a serious and irreversible
injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered
to be a potential therapy for I/R injury due to the paracrine effects.
High-mobility group box 1 (HMGB1) is a novel mediator in MSC and
regulates the response of inflammation injury. Signal Transduction and
Transcription Activator 3 (STAT3) is a critical transcription factor and
important for release of paracrine factors. However, the relationship
between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.
In vitro, Hypoxia/Reoxygenation injury model was established by
AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay
and morphology observation. Detection of apoptotic proteins and protein
expression of HMGB1 and STAT3 by Western blot. The conditioned medium of
MSC with or without LPS pretreatment was cocultured with H9c2 cells for
24h before hypoxia treatment and MSC showed obvious cardiomyocytes
protect role, as evidence by decreased apoptosis rate and improved cells
viability, and LPS pretreated MSC exhibited better protect role than
untreated MSC. However, such effect was abolished in HMGB1 deficiency
group, silencing HMGB1 decreased the secretion of VEGF, HGF, IGF, cell
viability, and the expression of STAT3. Furthermore, STAT3 silence
attenuated the protective effect of LPS in MSC. Collectively, these
findings suggested that LPS improved MSC-mediated cardiomyocytes
protection by HMGB1/STAT3 signaling.