ArticleStem cell research & therapy2014
Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt signaling.
Article in Stem cell research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Retraction: High Glucose Induced Oxidative Stress and Apoptosis in Cardiac Microvascular Endothelial Cells Are Regulated by FoxO3a.PloS one · 2026Article
- Challenges of mesenchymal stem cells in the clinical treatment of COVID-19.Cell and tissue research · 2024Review
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- β-lapachone regulates mammalian inositol pyrophosphate levels in an NQO1- and oxygen-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Preterm birth alters the feeding-induced activation of Akt signaling in the muscle of neonatal piglets.Pediatric research · 2023Article
- One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsPBiomolecules · 2023Article
- Nucleolar Architecture Is Modulated by a Small Molecule, the Inositol Pyrophosphate 5-InsPBiomolecules · 2023Article
- Whole BodyInternational journal of molecular sciences · 2022Article
- The Role of Hypoxia in Improving the Therapeutic Potential of Mesenchymal Stromal Cells. A Comparative Study From Healthy Lung and Congenital Pulmonary Airway Malformations in Infants.Frontiers in bioengineering and biotechnology · 2022Article
- InsPProceedings of the National Academy of Sciences of the United States of America · 2020Article
- FNDC5/irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction.Stem cell research & therapy · 2020Article
- Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases.Molecules (Basel, Switzerland) · 2020Review
- Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy.Stem cell research & therapy · 2019Article
- Protective Effect of Fat Extract on UVB-Induced PhotoagingOxidative medicine and cellular longevity · 2019Article
- Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs: role of autophagy.Stem cell research & therapy · 2018Article
- The inositol pyrophosphate pathway in health and diseases.Biological reviews of the Cambridge Philosophical Society · 2018Review
- Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling.Journal of cellular physiology · 2018Review
- hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway.Stem cell research & therapy · 2018Article
- IP6K1 Reduces Mesenchymal Stem/Stromal Cell Fitness and Potentiates High Fat Diet-Induced Skeletal Involution.Stem cells (Dayton, Ohio) · 2017Article
- Autophagy mediates the beneficial effect of hypoxic preconditioning on bone marrow mesenchymal stem cells for the therapy of myocardial infarction.Stem cell research & therapy · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBone marrow-derived mesenchymal stem cells (BM-MSCs) have been proposed as an ideal autologous stem cell source for cell-based therapy for myocardial infarction (MI). However, decreased viability and impaired function of aged MSCs hampered the therapeutic efficacy of engrafted MSCs, and the underlying mechanisms remain unclarified. Here, we investigated the role of inositol phosphates 6 kinase (IP6Ks) inhibition on the therapeutic efficacy of BM-MSCs and its underlying mechanism.
methodsBM-MSCs isolated from young (8-week-old) or aged (18-month-old) donor male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury with or without administration of inositol phosphates 6 kinase (IP6Ks) inhibitor TNP (10 μM). MSC apoptosis induced by H/SD was determined by flow cytometry and TUNEL assays. Protein expressions were evaluated by Western blot assay. Furthermore, the paracrine effects of MSCs were measured by reverse transcriptase-polymerized chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses.
resultsAged BM-MSCs exhibited more Inositol pyrophosphate 7 (IP7) production, compared with young BM-MSCs. Meanwhile, the expression of phospho-Akt (Thr308) was significantly decreased in the aged MSCs, resulting in enhanced Bad activation and decreased Bax/Bcl-2 ratio. Moreover, the apoptosis in aged BM-MSCs was increased, compared with young BM-MSCs. Furthermore, TNP administration significantly inhibited IP7 production and increased the phosphorylation of Akt under both normoxic and hypoxic conditions. Meanwhile, IP6Ks inhibition reduced apoptotic index of aged MSCs, associated with decreased expressions of pro-apoptotic proteins Bax and Bad and increased anti-apoptotic protein Bcl-2. The expressions of angiogenic factors, including VEGF, bFGF, IGF-1 and HGF, were decreased in MSCs from aged mice. In addition, TNP administration enhanced the paracrine efficiency of aged BM-MSCs under normoxic and hypoxic conditions.
conclusionsThis study demonstrates for the first time that IP6Ks and IP7 play critical role in the aging related vulnerability to hypoxic injury and impaired paracrine efficiency of BM-MSCs, which is associated with impaired Akt activation.
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