GW28-e0891 miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit+Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling

The low survival rate of cardiac stem cells (CSCs) in the infarcted myocardium hampers cell therapy for ischemic cardiomyopathy. MicroRNA-21 (miR-21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c-kit+CSC remain unclear. Thus, we hypothesized that miR-21 reduces hydrogen peroxide- (H2O2-) induced apoptosis in c-kit+CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR-21 mimics efficiently reduced H2O2-induced apoptosis in c-kit+CSC, as evidenced by the downregulation of the proapoptosis proteins caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2. In addition, the gain of function of miR-21 in c-kit+CSC downregulated the protein level of PTEN although its mRNA level changed slightly; in the meantime, miR-21 overexpression also increased phospho-Akt (p-Akt). The antiapoptotic effects of miR-21 were comparable with Phen (bpV), the selective inhibitor of PTEN, while miR-21 inhibitor or PI3K’s inhibitor LY294002 efficiently attenuated the antiapoptotic effect of miR-21. Taken together, these results indicate that the anti-H2O2-induced apoptosis effect of miR-21 in c-kit+CSC is contributed by PTEN/PI3K/Akt signaling. miR-21 could be a potential molecule to facilitate the c-kit+CSC therapy in ischemic myocardium.

Download Full-text

GW29-e1434 miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit+Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2018.08.161 ◽

2018 ◽

Vol 72 (16) ◽

pp. C43-C44

Author(s):

Bei Shi , WangYan

Keyword(s):

Hydrogen Peroxide ◽

Stem Cells ◽

Akt Signaling ◽

Cardiac Stem Cells ◽

Induced Apoptosis

Download Full-text

Wnt1 Inhibits Hydrogen Peroxide-Induced Apoptosis in Mouse Cardiac Stem Cells

PLoS ONE ◽

10.1371/journal.pone.0058883 ◽

2013 ◽

Vol 8 (3) ◽

pp. e58883 ◽

Cited By ~ 18

Author(s):

Jingjin Liu ◽

Yongshun Wang ◽

Wenjuan Du ◽

Wenhua Liu ◽

Fang Liu ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Stem Cells ◽

Cardiac Stem Cells ◽

Induced Apoptosis

Download Full-text

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

10.21203/rs.3.rs-74818/v1 ◽

2020 ◽

Author(s):

Han-You Wu ◽

Xiang-Cheng Zhang ◽

Ye Cao ◽

Kai Yan ◽

Jing-Yuan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mouse Model ◽

Signaling Pathways ◽

Akt Signaling ◽

Human Umbilical Cord ◽

Induced Apoptosis

Abstract Background: Human umbilical cord mesenchymal stem cells (hUCMSCs) transplantation has been proposed as a promising therapeutic approach for treating acute liver failure (ALF), but its application is limited by immune rejection and tumor formation. Exosomes contain various bioactive cargos including mRNA, microRNA, and protein that can alter the cellular enviroment to enhance tissue repair. However, the exact effects of hUCMSCs derived exosomes (hUCMSC-Exo) on the healing of ALF and their potential mechanisms are not explored.Methods: In vivo, mouse model of ALF were set up through a single intraperitoneal injection of acetaminophen (APAP, 380 mg/kg). In vitro, human hepatocyte cells LO2 were treated with APAP (5 mM). Then APAP-induced ALF mice and APAP-injured LO2 cells were treated with hUCMSC-Exo. Finally, the effects and the mechanisms were estimated.Results: We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Conclusions: Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways, suggesting that administration of hucMSC-Exo may be an alternative approach for the treatment of ALF.

Download Full-text

Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro

Journal of Cellular Biochemistry ◽

10.1002/jcb.24582 ◽

2013 ◽

Vol 114 (10) ◽

pp. 2346-2355 ◽

Cited By ~ 68

Author(s):

Fu-Wu Wang ◽

Zhen Wang ◽

Yan-Min Zhang ◽

Zhao-Xia Du ◽

Xiao-Li Zhang ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Protective Effect ◽

Marrow Mesenchymal Stem Cells ◽

Induced Apoptosis

Download Full-text

VEGF promotes cardiac stem cells differentiation into vascular endothelial cells via the PI3K/Akt signaling pathway

Artificial Cells Nanomedicine and Biotechnology ◽

10.3109/21691401.2013.837473 ◽

2013 ◽

Vol 42 (6) ◽

pp. 400-405 ◽

Cited By ~ 12

Author(s):

Nuan Xiao ◽

Xiao-Yong Qi ◽

Lu-Ning Tang ◽

Li-Li Tan ◽

Ya-Qing Chen ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Akt Signaling ◽

Cardiac Stem Cells ◽

Vascular Endothelial ◽

Akt Signaling Pathway

Download Full-text

Differential Expression of MicroRNA-19b Promotes Proliferation of Cancer Stem Cells by Regulating the TSC1/mTOR Signaling Pathway in Multiple Myeloma

Cellular Physiology and Biochemistry ◽

10.1159/000494821 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1804-1814 ◽

Cited By ~ 6

Author(s):

Ni Wang ◽

Xiaohua Liang ◽

Weijian Yu ◽

Shihang Zhou ◽

Meiyun Fang

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Cancer Stem Cells ◽

Real Time ◽

Caspase 3 ◽

In Silico Analysis ◽

Luciferase Assay ◽

Downstream Target ◽

Induced Apoptosis

Background/Aims: MiR-19b has been reported to be involved in several malignancies, but its role in multiple myeloma (MM) is still unknown. The objective of this study was to explore the biological mechanism of miR-19b in the progression of MM. Methods: First, we performed real-time polymerase chain reaction (PCR) and Western blot to study the expression of miR-19b, tuberous sclerosis 1 (TSC1), and caspase-3 in different groups. MTT assay was performed to explore the effect of miR-19b on survival and apoptosis of cancer stem cells (CSCs). Computation analysis and luciferase assay were utilized to confirm the interaction between miR-19b and TSC1. Results: A total of 38 participants comprising 20 subjects with MM and 18 healthy subjects as normal controls were enrolled in our study. Real-time PCR showed dramatic upregulation of miR-19b, but TSC1 was evidently suppressed in the MM group. MiR-19b overexpression substantially promoted clonogenicity and cell viability, and further inhibited apoptosis of CSCs in vitro. Furthermore, miR-19b overexpression downregulated the expression of caspase-3, which induced apoptosis. Using in silico analysis, we identified that TSC1 might be a direct downstream target of miR-19b, and this was further confirmed by luciferase assay showing that miR-19b apparently reduced the luciferase activity of wild-type TSC1 3´-UTR, but not that of mutant TSC1 3´-UTR. There was also evident decrease in TSC1 mRNA and protein in CSCs following introduction of miR-19b. Interestingly, reintroduction of TSC1 abolished the miR-19b-induced proliferation promotion and apoptosis inhibition in CSCs. Conclusion: These findings collectively suggest that miR-19b promotes cell survival and suppresses apoptosis of MM CSCs via targeting TSC1 directly, indicating that miR-19b may serve as a potential and novel therapeutic target of MM based on miRNA expression.

Download Full-text