Retracted: Protection of miR‐19b in hypoxia/reoxygenation‐induced injury by targeting PTEN

Liu, Wan‐Gen; Han, Lili; Xiang, Rong

doi:10.1002/jcp.28286

Cited by 13 publications

(9 citation statements)

References 47 publications

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“…The pharmacological inhibition of PTEN can further protect H9C2 cells from apoptosis in the context of hypoxia when used in combination with MSC-derived exosomes or miR-144 mimics. Other studies have also indicated that miRNAs can protect against hypoxiainduced cell apoptosis by inhibiting PTEN and targeting the AKT signaling pathway [39,40]. These findings further support the conclusion that MSC-derived exosomes exert anti-apoptotic effects on hypoxic CMCs by delivering miR-144 to cells where it targets the PTEN/ AKT pathway (Additional file 2: Figure S1).…”

Section: Discussionsupporting

confidence: 78%

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Wen¹,

Mai²,

Zhu³

et al. 2020

Stem Cell Res Ther

126

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Background: A growing body of evidence suggests that stem cell-derived exosomal microRNAs (miRNAs) could be a promising cardioprotective therapy in the context of hypoxic conditions. The present study aims to explore how miRNA-144 (miR-144), a miRNA contained in bone marrow mesenchymal stem cell (MSC)-derived exosomes, exerts a cardioprotective effect on cardiomyocyte apoptosis in the context of hypoxic conditions and identify the underlying mechanisms. Methods: MSCs were cultured using the whole bone marrow adherent method. MSC-derived exosomes were isolated using the total exosome isolation reagent and confirmed by nanoparticle trafficking analysis as well as western blotting using TSG101 and CD63 as markers. The hypoxic growth conditions for the H9C2 cells were established using the AnaeroPack method. Treatment conditions tested included H9C2 cells pre-incubated with exosomes, transfected with miR-144 mimics or inhibitor, or treated with the PTEN inhibitor SF1670, all under hypoxic growth conditions. Cell apoptosis was determined by flow cytometry using 7-ADD and Annexin V together. The expression levels of the miRNAs were detected by real-time PCR, and the expression levels of AKT/p-AKT, Bcl-2, caspase-3, HIF-1α, PTEN, and Rac-1 were measured by both real-time PCR and western blotting. Results: Exosomes were readily internalized by H9C2 cells after co-incubation for 12 h. Exosome-mediated protection of H9C2 cells from apoptosis was accompanied by increasing levels of p-AKT. MiR-144 was found to be highly enriched in MSC-derived exosomes. Transfection of cells with a miR-144 inhibitor weakened exosomemediated protection from apoptosis. Furthermore, treatment of cells grown in hypoxic conditions with miR-144 mimics resulted in decreased PTEN expression, increased p-AKT expression, and prevented H9C2 cell apoptosis, whereas treatment with a miR-144 inhibitor resulted in increased PTEN expression, decreased p-AKT expression, and enhanced H9C2 cell apoptosis in hypoxic conditions. We also validated that PTEN was a target of miR-144 by using luciferase reporter assay. Additionally, cells treated with SF1670, a PTEN-specific inhibitor, resulted in increased p-AKT expression and decreased H9C2 cell apoptosis. Conclusions: These findings demonstrate that MSC-derived exosomes inhibit cell apoptotic injury in hypoxic conditions by delivering miR-144 to cells, where it targets the PTEN/AKT pathway. MSC-derived exosomes could be a promising therapeutic vehicle to facilitate delivery of miRNA therapies to ameliorate ischemic conditions.

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Section: Discussionsupporting

confidence: 78%

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Wen¹,

Mai²,

Zhu³

et al. 2020

Stem Cell Res Ther

126

View full text Add to dashboard Cite

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“… 40 Restoring miR-19b reduces cell apoptosis and expedites the viability as well as increased Bcl-2/Bax ratios in H/R-induced PC12 and BV2 cells. 41 Except that, our study also indicated that inhibition of miR-19b in exosomes increased levels of IL-6 and decreased levels of IL-10. Li et al have supported that transfection of miR-19 inhibitor promotes release of cytokines IL-6 in fibroblast-like synoviocytes.…”

Section: Discussionsupporting

confidence: 52%

Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal microRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1/TGF-β Signaling Axis

Cao¹,

Chen²,

Zhang³

et al. 2020

CCID

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Introduction Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs-derived exosomes on skin wound healing. Methods ADMSCs were extracted and ADMSCs-derived exosomes were identified. Skin damage models were established by treating HaCaT cells and human skin fibroblasts with H 2 O 2 . Next, the roles of ADMSCs and their derived exosomes were investigated. The exosomal miRNA then was analyzed, and the function of miRNA on the H 2 O 2 -induced cells was studied by miRNA suppression. Bioinformatics analysis, luciferase activity and RIP assays were implemented to find the target genes ofthe miRNA and the modulated pathways. A mouse skin damage model was induced to elucidate the effects of exosomes in vivo by injecting exosomes. Results H 2 O 2 treatment significantly reduced the viability of HaCaT cells and increased their apoptosis rate. Co-culture with ADMSCs or their derived exosomes could improve the cell damage caused by H 2 O 2 . Meanwhile, H 2 O 2 treatment promoted the internalization of exosomes. ADMSCs and their derived exosomes significantly increased miR-19b expression in the recipient cells, while inhibiting miR-19b resulted in a reduction in the therapeutic effect of ADMSCs-derived exosomes. Besides, miR-19b regulated the TGF-β pathway by targeting CCL1. The therapeutic effect of exosomes was further confirmed by a mouse model of skin damage. Conclusion Our study indicates that exosomal miR-19b derived from ADMSCs regulates the TGF-β pathway by targeting CCL1, thereby promoting the healing of skin wounds.

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“…As it was reported previously, PTEN gene is one of the main negative regulators of PI3K/Akt pathway, and inhibition of PTEN can facilitate intrinsic regenerative outgrowth of adult peripheral axons [42]; from well-documented papers, we screened out several miRs that implicated with PTEN downregulation and neuronal repair. The literature on EVs suggested that miR candidates, such as miR-19b [43], miR-21 [40], miR-29b-3p [44], miR-233 [45], and miR-304-5p [46], would enable the activation of PI3K and downstream signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells

Shen

et al. 2021

Stem Cell Res Ther

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Background Patients with peripheral nerve injury (PNI) often suffer from hypoxic ischemic impairments, in particular when combined with vascular damage, causing neuronal dysfunction and death. Increasing attention has been paid on skin precursor-derived Schwann cells (SKP-SCs), and previous study has shown that SKP-SCs could promote sensory recovery after cell therapy for PNI, resembling the effect of naive SCs, and SKP-SC-derived extracellular vesicles (SKP-SC-EVs) are putatively supposed to be promising therapeutic agents for neural regeneration. Methods SKPs were induced to differentiate towards SCs with cocktail factors (N2, neuregulin-1β, and forskolin) in vitro. SKP-SC-EVs were isolated by exoEasy Maxi Kit and characterized by morphology and phenotypic markers of EVs. Rat sensory neurons from dorsal root ganglions (DRGs) were primarily cultured in regular condition or exposed to oxygen-glucose-deprivation (OGD) condition. SKP-SC-EVs were applied to DRGs or sensory neurons, with LY294002 (a PI3K inhibitor) added; the effect on neurite outgrowth and cell survival was observed. Moreover, microRNA (miR) candidate contained in SKP-SC-EVs was screened out, and miR-mimics were transfected into DRG neurons; meanwhile, the negative regulation of PTEN/PI3K/Akt axis and downstream signaling molecules were determined. Results It was shown that SKP-SC-EVs could improve the neurite outgrowth of DRGs and sensory neurons. Furthermore, SKP-SC-EVs enhanced the survival of sensory neurons after OGD exposure by alleviating neuronal apoptosis and strengthening cell viability, and the expression of GAP43 (a neuron functional protein) in neurons was upregulated. Moreover, the neuro-reparative role of SKP-SC-EVs was implicated in the activation of PI3K/Akt, mTOR, and p70S6k, as well as the reduction of Bax/Bcl-2 ratio, that was compromised by LY294002 to some extent. In addition, transferring miR-21-5p mimics into sensory neurons could partly protect them from OGD-induced impairment. Conclusions Sum up, SKP-SC-EVs could improve neurite outgrowth of DRG sensory neurons in physiological and pathological condition. Moreover, the in vitro therapeutic potential of SKP-SC-EVs on the survival and restoration of OGD-injured sensory neurons was evidenced to be associated with miR-21-5p contained in the small EVs and miR-21-5p/PTEN/PI3K/Akt axis. Graphic abstract

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Retracted: Protection of miR‐19b in hypoxia/reoxygenation‐induced injury by targeting PTEN

Cited by 13 publications

References 47 publications

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway

<p>Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal microRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1/TGF-β Signaling Axis</p>

Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells

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