Protein phosphatase 2A plays an important role in migration of bone marrow stroma cells

Chen, Weiqian; Wang, Shizhen; Xia, Jun; Huang, Zan; Tu, Xin; Shen, Zhenya

doi:10.1007/s11010-015-2624-7

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…The cells were then trypsinized and frozen in liquid nitrogen for later use. The enriched MSC population was characterized with antibodies against CD29, CD44, CD45, CD90, CD117, Sca-1, and their relative isotype controls on a flow cytometry (Millipore Guava easyCyte) as previously described [10].…”

Section: Methodsmentioning

confidence: 99%

Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model

Han¹,

Cui²,

Li³

et al. 2019

Stem Cell Res Ther

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BackgroundCell therapy remains the most promising approach against ischemic heart injury. However, poor survival of engrafted cells in ischemic sites diminishes its therapeutic efficacy. Follistatin-like 1 (Fstl1) is documented as a novel pro-survival cardiokine for cardiomyocytes, and it is protective during ischemic heart injury. In the present study, we characterize the potential of Fstl1 as an effective strategy to enhance hypoxia resistance of donor cells and optimize stem cell-based therapy.MethodsMurine bone marrow-derived mesenchymal stem cells (MSCs) were expanded in monolayer culture and characterized by flow cytometry. MSCs were subjected to hypoxia to mimic cardiac ischemic environment. Expression of Fstl1 was monitored 0, 24, and 48 h following hypoxia. Constitutive expression of Fstl1 in MSCs was achieved by lentivirus-mediated Fstl1 overexpression. Genetically modified MSCs were further collected for cell death and proliferation assay following 48 h of hypoxic treatment. Acute myocardial infarction (MI) model was created by ligating the left anterior descending coronary artery, while control MSCs (MSCs-mCherry) or Fstl1-overexpressing MSCs (MSCs-Fstl1) were injected into the peri-infarct zone simultaneously. Subsequently, retention of the donor cells was evaluated on post-therapy 1, 3, & 7 days. Finally, myocardial function, infarct size, inflammation, and neovascularization of the infarcted hearts were calculated thereafter.ResultsExpression of Fstl1 in hypoxic MSCs declines dramatically in a time-dependent manner. In vitro study further demonstrated that Fstl1 promotes survival and proliferation of hypoxic MSCs. Moreover, Fstl1 significantly prolongs MSC survival/retention after implantation. Finally, transplantation with Fstl1-overexpressing MSCs significantly improves post-MI cardiac function by limiting scar formation, reducing inflammatory response, and enhancing neovascularization.ConclusionsOur results suggest Fstl1 is an intrinsic cardiokine promoting survival and proliferation of MSCs, thereby optimizing their engraftment and therapeutic efficacy during cell therapy.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1111-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model

Han¹,

Cui²,

Li³

et al. 2019

Stem Cell Res Ther

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“…Cell viability was evaluated by CCK-8 assay (Dojindo Laboratories, Japan) as described previously [ 26 ]. Briefly, MSCs in 96-well plates were transfected with miR-133 agomir/antagomir and cultured for 6, 12, 24, and 48 h. The culture supernatants were then changed to fresh medium with 10% CCK-8 (Dojindo Laboratories, Japan).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction

et al. 2017

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Background: Our study aim was to evaluate the therapeutic efficacy and mechanisms of miR-133-overexpressing mesenchymal stem cells (MSCs) on acute myocardial infarction. Methods: Rat MSCs were isolated and purified by whole bone marrow adherent culturing. After transfection with the agomir or antagomir of miR-133, MSCs were collected for assay of cell vitality, apoptosis, and cell cycle progression. At the same time, exosomes were isolated from the supernatant to analyze the paracrine miR-133. For in-vivo studies, constitutive activation of miR-133 in MSCs was achieved by lentivirus-mediated miR-133 overexpression. A rat myocardial infarction model was created by ligating the left anterior descending coronary artery, while control MSCs (vector-MSCs) or miR-133-overexpressed MSCs (miR-133-MSCs) were injected into the zone around the myocardial infarction. Subsequently, myocardial function was evaluated by echocardiography on days 7 and 28 post infarction. Finally the infarcted hearts were collected on days 7 and 28 for myocardial infarct size measurement and detection of snail 1 expression. Results: Hypoxia-induced apoptosis of MSCs obviously reduced, along with enhanced expression of total poly ADP-ribose polymerase protein, after miR-133 agomir transfection, while the apoptosis rate increased in MSCs transfected with miR-133 antagomir. However, no change in cell viability and cell-cycle distribution was observed in control, miR-133-overexpressed, and miR-133-interfered MSCs. Importantly, rats transplanted with miR-133-MSCs displayed more improved cardiac function after acute myocardial infarction, compared with those that received vector-MSC injection. Further studies indicated that cardiac expression of snail 1 was significantly repressed by adjacent miR-133-overexpressing MSCs, and both the inflammatory level and the infarct size decreased in miR-133-MSC-injected rat hearts.

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“…B and C). The increase on basal phosphorylation on tested proteins in Fyn‐deficient cells, together with our recent finding indicating that Fyn kinase controls the activity of PP2A in mast cells , led us to test if a defective activity of PP2A could be involved in the observed phenotype, since this phosphatase plays an important role in the migration of immune cells .…”

Section: Resultsmentioning

confidence: 99%

Fyn kinase mediates cortical actin ring depolymerization required for mast cell migration in response to TGF‐β in mice

et al. 2017

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Transforming growth factor-β (TGF-β) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-β-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-β-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-β was impaired in the absence of the kinase. TGF-β caused depolymerization of the cortical actin ring and changes on the phosphorylation of cofilin, LIMK and CAMKII only in WT cells. Defective cofilin activation and phosphorylation of regulatory proteins was detected in Fyn-deficient BMMCs and this finding correlated with a lower activity of the catalytic subunit of the phosphatase PP2A. Diminished TGF-β-induced chemotaxis of Fyn-deficient cells was also observed in an in vivo model of MC migration (bleomycin-induced scleroderma). Our results show that Fyn kinase is an important positive effector of TGF-β-induced chemotaxis through the control of PP2A activity and this is relevant to pathological processes that are related to TGF-β-dependent mast cell migration.

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Protein phosphatase 2A plays an important role in migration of bone marrow stroma cells

Cited by 12 publications

References 44 publications

Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model

Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model

MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction

Fyn kinase mediates cortical actin ring depolymerization required for mast cell migration in response to TGF‐β in mice

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