Valsartan impairs angiogenesis of mesenchymal stem cells through Akt pathway

2013 ◽  
Vol 167 (6) ◽  
pp. 2765-2774 ◽  
Author(s):  
Cheng-I Cheng ◽  
Chang-Chun Hsiao ◽  
Shinn-Chih Wu ◽  
Shao-Yu Peng ◽  
Hon-Kan Yip ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Akt Pathway

scholarly journals Human Mesenchymal Stem Cells Derived Exosomes Inhibit the Growth of Acute Myeloid Leukemia Cells via Regulating miR-23b-5p/TRIM14 Pathway

2021 ◽  
Author(s):  
hui cheng ◽  
Jie Ding ◽  
Gusheng Tang ◽  
Aijie Huang ◽  
Lei Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Mesenchymal Stem Cells ◽  
Myeloid Leukemia ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a malignancy commonly seen in adults. Previous studies indicated that TRIM14 played a tumorigenic role in various types of cancer and miR-23b-5p was down-regulated in human mesenchymal stem cell-derived exosomes (HMSC-exos) of AML patients. However, their roles in AML remains unclear. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML.Materials and methods: The blood specimen was collected from AML patients and healthy donators. Exosomes were extracted from the culture medium of human mesenchymal stem cells under ultracentrifugation. Then exosomes were co-cultured with AML cells to determine the effect of their contents. The cell proliferation was detected by cell counting kit-8 assay, whereas the cell apoptosis was detected by flow cytometry. The expression of miR-23b-5p and TRIM14 was silenced or overexpressed to explore their biological functions in AML. Luciferase reporter assay was conducted to validate the interaction between miR-23b-5p and TRIM14. Gene expression was determined by quantitative real-time PCR and immunoblots.Results: TRIM14 was significantly increased in AML patients and cell lines. The inhibition of TRIM14 significantly reduced the proliferation and induced the apoptosis of AML cells via activating PI3K/AKT pathway, whereas its overexpression exhibited reversed effects. HMSC-exos could suppress the proliferation of AML cells through the delivery of miR-23b-5p. Moreover, miR-23b-5p inhibited the transcription of TRIM14 by binding on its 3’UTR region. Overexpression of TRIM14 exhibited reversed effect against the function of miR-23b-5p mimic.Conclusion: TRIM14 could promote the proliferation of AML cells via activating PI3K/AKT pathway, which was reversed by HMSC-exos through delivering miR-23b-5p. These findings indicated that miR-23b-5p and TRIM14 could be applied as potential targets for the treatment of AML.

scholarly journals Upregulation of PTEN in Glioma Cells by Cord Blood Mesenchymal Stem Cells Inhibits Migration via Downregulation of the PI3K/Akt Pathway

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e10350 ◽  
Author(s):  
Venkata Ramesh Dasari ◽  
Kiranpreet Kaur ◽  
Kiran Kumar Velpula ◽  
Meena Gujrati ◽  
Daniel Fassett ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Glioma Cells ◽  
Akt Pathway

Lin28 Enhances Glucose Metabolism in Human Placental Mesenchymal Stem Cells during Hypoxia via the PI3K-Akt Pathway

2021 ◽  
Author(s):  
Xi Zhou ◽  
Junbo Li ◽  
Jin Wang ◽  
Huifang Yang ◽  
Jingzeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Glucose Metabolism ◽  
Ischemia Reperfusion ◽  
Stem Cell Differentiation ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Western Blots ◽  
Hypoxic Conditions

Abstract Mesenchymal stem cells (MSCs) are widely used to treat and prevent liver ischemia–reperfusion injury (LIRI), which commonly occurs after liver surgery. Lin28 is an RNA-binding protein crucial for early embryonic development, stem cell differentiation/reprogramming, tumorigenesis, and metabolism. However, whether Lin28 can enhance metabolism in human placental MSCs (PMSCs) during hypoxia to improve the protective effect against LIRI remains unclear. First, a Lin28 overexpression construct was introduced into PMSCs; glucose metabolism, the expression of glucose metabolism - and PI3K-AKT pathway-related proteins, and the levels of microRNA Let-7 family members were examined using a glucose metabolism kit, western blots, and real-time quantitative PCR, respectively. Next, treatment with an AKT inhibitor was performed to understand the association of Lin28 with the PI3K-Akt pathway. Subsequently, AML12 cells were co-cultured with PMSCs to construct an in vitro model of PMSC protecting liver cells from hypoxia injury. Finally, C57BL/6J mice were used to establish a partial warm hepatic ischemia–reperfusion model in vivo. Lin28 increased the glycolysis capacity of PMSCs, allowing these cells to produce more energy under hypoxic conditions. Lin28 also activated PI3K-Akt signaling under hypoxic conditions, and AKT inhibition attenuated the effects of Lin28. In addition, Lin28 overexpression was found to protect cells against LIRI-induced liver damage, inflammation, and apoptosis and attenuate hypoxia-induced hepatocyte injury. Inconclusion, Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby providing protective effects against LIRI via the activation of the PI3K-Akt signaling pathway. Our study first reported the application of gene-modified mesenchymal stem cell-based therapy in LIRI.

scholarly journals The PI3k/Akt Pathway Is Associated With Angiogenesis, Oxidative Stress and Survival of Mesenchymal Stem Cells in Pathophysiologic Condition in Ischemia

2019 ◽  
pp. S131-S138 ◽  
Author(s):  
A. SAMAKOVA ◽  
A. GAZOVA ◽  
N. SABOVA ◽  
S. VALASKOVA ◽  
M. JURIKOVA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biologically Active ◽  
Akt Pathway ◽  
First Choice ◽  
Ischemic Diseases

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

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