Donor MSCs release apoptotic bodies to improve myocardial infarction via autophagy regulation in recipient cells.

Abstract:

:Mesenchymal stem cell (MSC) transplantation has been widely applied as a potential therapeutic for multiple diseases. However, the underlying therapeutic mechanisms are not fully understood, especially the paradox between the low survival rate of transplanted cells and the beneficial therapeutic effects generated by these cells. Herein, in a myocardial infarction (MI) model, we found that transplanted MSCs released apoptotic bodies (ABs) to enhance angiogenesis and improve cardiac functional reclovery via regulating macroautophagy/autophagy in the recipient endothelial cells (ECs). Mechanistically, after local transplantation, MSCs underwent extensive apoptosis in the short term and released ABs, which were engulfed by the recipient ECs. Then, in the ECs, ABs activated lysosome functions and promoted the expression of TFEB (transcription factor EB), which is a master gene in lysosomal biogenesis and autophagy. Finally, the increase in TFEB enhanced autophagy-related gene expression in ECs and promoted angiogenesis and cardiac functional recovery after MI. Collectively, we found that apoptotic donor MSCs promote angiogenesis via regulating autophagy in the recipient ECs, unveiling the role of donor cell apoptosis in the therapeutic effects generated by cell transplantation. Abbreviations: 3-MA: 3-methyladenine; ABs: apoptotic bodies; BECN1: beclin 1; CASP3: caspase 3; CQ: chloroquine; ECs: endothelial cells; EVs: extracellular vesicles; LAMP1: lysosomal-associated membrane protein 1; LVEF: left ventricular ejection fraction; LVFS: left ventricular fractional shortening; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MI: myocardial infarction; MSC: mesenchymal stem cell; NO: nitric oxide; TFEB: transcription factor EB; TUNEL: TdT-mediated dUTP Nick-End Labeling.

journal_name

Autophagy

journal_title

Autophagy

authors

Liu H,Liu S,Qiu X,Yang X,Bao L,Pu F,Liu X,Li C,Xuan K,Zhou J,Deng Z,Liu S,Jin Y

doi

10.1080/15548627.2020.1717128

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

2140-2155

issue

12

eissn

1554-8627

issn

1554-8635

journal_volume

16

pub_type

杂志文章
  • The Golgi as a potential membrane source for autophagy.

    abstract::In macroautophagy (hereafter autophagy), a morphological hallmark is the formation of double-membrane vesicles called autophagosomes that sequester and deliver cytoplasmic components to the lysosome/vacuole for degradation. This process begins with an initial sequestering compartment, the phagophore, which expands int...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13009

    authors: Geng J,Klionsky DJ

    更新日期:2010-10-01 00:00:00

  • The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

    abstract::The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by ...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.6.1.10817

    authors: Morselli E,Maiuri MC,Markaki M,Megalou E,Pasparaki A,Palikaras K,Criollo A,Galluzzi L,Malik SA,Vitale I,Michaud M,Madeo F,Tavernarakis N,Kroemer G

    更新日期:2010-01-01 00:00:00

  • MLKL contributes to Western diet-induced liver injury through inhibiting autophagy.

    abstract::Macroautophagy/autophagy is critical in maintaining cellular functions and homeostasis. Dynamic regulation of autophagy is associated with development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); however, the mechanisms involved in the regulation of autophagy in NAFLD/NASH are n...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1760624

    authors: Wu X,Nagy LE

    更新日期:2020-07-01 00:00:00

  • Caspase activation regulates the extracellular export of autophagic vacuoles.

    abstract::The endothelium plays a central role in the regulation of vascular wall cellularity and tone by secreting an array of mediators of importance in intercellular communication. Nutrient deprivation of human endothelial cells (EC) evokes unconventional forms of secretion leading to the release of nanovesicles distinct fro...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.19768

    authors: Sirois I,Groleau J,Pallet N,Brassard N,Hamelin K,Londono I,Pshezhetsky AV,Bendayan M,Hébert MJ

    更新日期:2012-06-01 00:00:00

  • An insight into the mechanistic role of p53-mediated autophagy induction in response to proteasomal inhibition-induced neurotoxicity.

    abstract::The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are the two most important components of cellular mechanisms for protein degradation. In the present study we investigated the functional relationship of the two systems and the interactional role of p53 in vitro. Our study showed that the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.5.8377

    authors: Du Y,Yang D,Li L,Luo G,Li T,Fan X,Wang Q,Zhang X,Wang Y,Le W

    更新日期:2009-07-01 00:00:00

  • UCHL1 deficiency exacerbates human islet amyloid polypeptide toxicity in β-cells: evidence of interplay between the ubiquitin/proteasome system and autophagy.

    abstract::The islet in type 2 diabetes mellitus (T2DM) is characterized by a deficit in β-cells and increased β-cell apoptosis attributable at least in part to intracellular toxic oligomers of IAPP (islet amyloid polypeptide). β-cells of individuals with T2DM are also characterized by accumulation of polyubiquitinated proteins ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.28478

    authors: Costes S,Gurlo T,Rivera JF,Butler PC

    更新日期:2014-06-01 00:00:00

  • Identification of the autophagy pathway in a mollusk bivalve, Crassostrea gigas.

    abstract::The Pacific oyster, Crassostrea gigas, is a mollusk bivalve commercially important as a food source. Pacific oysters are subjected to stress and diseases during culture. The autophagy pathway is involved in numerous cellular processes, including responses to starvation, cell death, and microorganism elimination. Autop...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1713643

    authors: Picot S,Faury N,Arzul I,Chollet B,Renault T,Morga B

    更新日期:2020-11-01 00:00:00

  • A role for TOR complex 2 signaling in promoting autophagy.

    abstract::The conserved target of rapamycin (TOR) kinase is a central regulator of cell growth in response to nutrient availability. TOR forms 2 structurally and functionally distinct complexes, TORC1 and TORC2, and negatively regulates autophagy via TORC1. Here we demonstrate TOR also operates independently through the TORC2 s...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.36262

    authors: Vlahakis A,Powers T

    更新日期:2014-01-01 00:00:00

  • Macroautophagy: protector in the diabetes drama?

    abstract::Macroautophagy ("autophagy") is regulated by the same insulin-amino acid-mTOR signaling pathway that controls protein synthesis. Although the literature does not so far include any direct studies confirming this, we expect autophagy to increase during insulin resistance. We discuss the possibility that this may be a u...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4449

    authors: Meijer AJ,Codogno P

    更新日期:2007-09-01 00:00:00

  • Tipping the delicate balance: defining how proteasome maturation affects the degradation of a substrate for autophagy and endoplasmic reticulum associated degradation (ERAD).

    abstract::An increasing body of data links endoplasmic reticulum (ER) function to autophagy. Not surprisingly, then, some aberrant proteins in the ER can be destroyed either via ER associated degradation (ERAD), which is proteasome-mediated, or via autophagy. One such substrate is the "Z" variant of the alpha-1 protease inhibit...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4906

    authors: Brodsky JL,Scott CM

    更新日期:2007-11-01 00:00:00

  • Friend or food: different cues to the autophagosomal proteome.

    abstract::A hallmark of macroautophagy is the formation of autophagosomes, double-membrane vesicles that enwrap cellular components destined for lysosomal degradation. We examined autophagosomal protein dynamics under various inducing stimuli using a comprehensive mass spectrometry-based proteomics approach in combination with ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.20286

    authors: Becker AC,Bunkenborg J,Eisenberg T,Harder LM,Schroeder S,Madeo F,Andersen JS,Dengjel J

    更新日期:2012-06-01 00:00:00

  • Manipulation of autophagy by MIR375 generates antitumor effects in liver cancer.

    abstract::The exploration into the roles of autophagy in tumorigenesis, either as tumor suppressor or tumor promoter, has led to a great increase in the knowledge of cancer development, progression and treatment. However, there is currently no consensus on how to manipulate autophagy to improve antitumor effects. In this study,...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21796

    authors: Chang Y,Lin J,Tsung A

    更新日期:2012-12-01 00:00:00

  • Autophagy controls neonatal myogenesis by regulating the GH-IGF1 system through a NFE2L2- and DDIT3-mediated mechanism.

    abstract::Macroautophagy/autophagy is emerging as an important process in adult muscle stem cells functions: it regulates metabolic reprogramming during activation from a quiescent state, maintains stemness and prevents senescence. We now show that autophagy is specifically required for neonatal myogenesis and muscle developmen...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1507439

    authors: Zecchini S,Giovarelli M,Perrotta C,Morisi F,Touvier T,Di Renzo I,Moscheni C,Bassi MT,Cervia D,Sandri M,Clementi E,De Palma C

    更新日期:2019-01-01 00:00:00

  • One step closer to understanding mammalian macroautophagy initiation: Interplay of 2 HORMA architectures in the ULK1 complex.

    abstract::ULK1 and ATG13 assemble with RB1CC1/FIP200 and ATG101 to form a macroautophagy (hereafter autophagy) induction (ULK1) complex in higher eukaryotes. The yeast counterpart, the Atg1 complex, is comprised of Atg1 and Atg13 (ULK1 and ATG13 homologs), Atg17 (a proposed functional homolog of RB1CC1), and either the Atg101 s...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1087635

    authors: Popelka H,Klionsky DJ

    更新日期:2015-11-02 00:00:00

  • Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome.

    abstract::There is overwhelming evidence for an association between impaired mitochondrial function and metabolic syndrome. Mitophagy, a process that selectively removes damaged mitochondria via a specialized form of autophagy, is essential for mitochondrial quality control (mitochondrial QC) and metabolic homeostasis. We thus ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1596482

    authors: Wu H,Wang Y,Li W,Chen H,Du L,Liu D,Wang X,Xu T,Liu L,Chen Q

    更新日期:2019-11-01 00:00:00

  • When more is less: excess and deficiency of autophagy coexist in skeletal muscle in Pompe disease.

    abstract::The role of autophagy, a catabolic lysosome-dependent pathway, has recently been recognized in a variety of disorders, including Pompe disease, which results from a deficiency of the glycogen-degrading lysosomal hydrolase acid-alpha glucosidase (GAA). Skeletal and cardiac muscle are most severely affected by the progr...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.1.7293

    authors: Raben N,Baum R,Schreiner C,Takikita S,Mizushima N,Ralston E,Plotz P

    更新日期:2009-01-01 00:00:00

  • Minocycline inhibits the growth of glioma by inducing autophagy.

    abstract::Minocycline has been shown to alleviate several neurological disorders. Unexpectedly, we found that minocycline had opposite effects on glioma cells: minocycline induced nonapoptotic cell death in glioma cells. The glioma cell death was associated with the presence of autophagic vacuoles in the cytoplasm. Minocycline ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.2.14043

    authors: Liu WT,Lin CH,Hsiao M,Gean PW

    更新日期:2011-02-01 00:00:00

  • Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome.

    abstract::Based on a functional categorization, proteins may be grouped into three types and sorted to either the proteasome or the macroautophagy pathway for degradation. The two pathways are mechanistically connected but their capacity seems different. Macroautophagy can degrade all forms of misfolded proteins whereas proteas...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.5190

    authors: Ding WX,Yin XM

    更新日期:2008-02-01 00:00:00

  • Downregulation of autophagy through CUL3-KLHL20-mediated turnover of the ULK1 and PIK3C3/VPS34 complexes.

    abstract::The molecular mechanism of macroautophagy/autophagy induction has been intensively studied, but little is known about downregulation of autophagy and how this process is restricted. In particular, how is autophagy maintained at an appropriate homeostatic level when cells are subjected to prolonged stress? In this stud...

    journal_title:Autophagy

    pub_type: 评论,社论

    doi:10.1080/15548627.2016.1173802

    authors: Feng Y,Klionsky DJ

    更新日期:2016-07-02 00:00:00

  • AMPK connects energy stress to PIK3C3/VPS34 regulation.

    abstract::The class III phosphatidylinositol (PtdIns)-3 kinase, PIK3C3/VPS34, forms multiple complexes and regulates a variety of cellular functions, especially in intracellular vesicle trafficking and autophagy. Even though PtdIns3P, the product of PIK3C3, is thought to be a critical membrane marker for the autophagosome, it i...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.24877

    authors: Kim J,Guan KL

    更新日期:2013-07-01 00:00:00

  • Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages.

    abstract::Phagocytosis of naturally dying cells usually blocks inflammatory reactions in host cells. We have recently observed that clearance of cells dying through autophagy leads to a pro-inflammatory response in human macrophages. Investigating this response further, we found that during engulfment of MCF-7 or 293T cells und...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.3.14583

    authors: Petrovski G,Ayna G,Majai G,Hodrea J,Benko S,Mádi A,Fésüs L

    更新日期:2011-03-01 00:00:00

  • Inhibitory effect of intracellular lipid load on macroautophagy.

    abstract::Degradation of intracellular components via macroautophagy is a complex multistep process that starts with the sequestration of cytosolic cargo in a de novo formed double-membrane vesicle or autophagosome. This compartment acquires the hydrolases required for cargo digestion by fusion with lysosomes. In contrast to th...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1096/fj.09-144519

    authors: Koga H,Kaushik S,Cuervo AM

    更新日期:2010-08-01 00:00:00

  • The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.

    abstract::The proteasome inhibitor bortezomib has shown remarkable clinical success in the treatment of multiple myeloma. However, the efficacy and mechanism of action of bortezomib in solid tumor malignancies is less well understood. In addition, the use of this first-in-class proteasome inhibitor is limited by several factors...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.22185

    authors: Zang Y,Thomas SM,Chan ET,Kirk CJ,Freilino ML,DeLancey HM,Grandis JR,Li C,Johnson DE

    更新日期:2012-12-01 00:00:00

  • Targeted therapy for the loss of von Hippel-Lindau in renal cell carcinoma: a novel molecule that induces autophagic cell death.

    abstract::Radiation and conventional cytotoxic chemotherapies are ineffective in treating renal cancer. Approximately 75 percent of renal cell carcinoma (RCC) is associated with an inactivation of the tumor suppressor gene von Hippel-Lindau (VHL). We exploited the possibility of targeting VHL-deficient RCC through synthetic let...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6785

    authors: Turcotte S,Sutphin PD,Giaccia AJ

    更新日期:2008-10-01 00:00:00

  • ATG5 regulates plasma cell differentiation.

    abstract::Autophagy is a conserved homeostatic process in which cytoplasmic contents are degraded and recycled. Two ubiquitin-like conjugation pathways are required for the generation of autophagosomes, and ATG5 is necessary for both of these processes. Studies of mice deficient in ATG5 reveal a key role for autophagy in T lymp...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.23484

    authors: Conway KL,Kuballa P,Khor B,Zhang M,Shi HN,Virgin HW,Xavier RJ

    更新日期:2013-04-01 00:00:00

  • Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection.

    abstract::Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1058683

    authors: Janda E,Lascala A,Carresi C,Parafati M,Aprigliano S,Russo V,Savoia C,Ziviani E,Musolino V,Morani F,Isidoro C,Mollace V

    更新日期:2015-01-01 00:00:00

  • Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1.

    abstract::Microglia are innate immune cells in the central nervous system (CNS), that supplies neurons with key factors for executing autophagosomal/lysosomal functions. Macroautophagy/autophagy is a cellular catabolic process that maintains cell balance in response to stress-related stimulation. Abnormal autophagy occurs with ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1522467

    authors: Li Y,Zhou D,Ren Y,Zhang Z,Guo X,Ma M,Xue Z,Lv J,Liu H,Xi Q,Jia L,Zhang L,Liu Y,Zhang Q,Yan J,Da Y,Gao F,Yue J,Yao Z,Zhang R

    更新日期:2019-03-01 00:00:00

  • A second report from the EMBO conference on autophagy: mechanism, regulation and selectivity of autophagy.

    abstract::Some key questions being examined in the field of autophagy concern the origin of the membrane that forms the sequestering vesicle, the function of the related machinery, including the identification of new components and binding partners of previously identified autophagy-related proteins and the mechanism of autopha...

    journal_title:Autophagy

    pub_type:

    doi:10.4161/auto.6.1.10819

    authors: Vellai T,Klionsky DJ

    更新日期:2010-01-01 00:00:00

  • Unconventional autophagy mediated by the WD40 domain of ATG16L1 is derailed by the T300A Crohn disease risk polymorphism.

    abstract::A coding polymorphism of the critical autophagic effector ATG16L1 (T300A) increases the risk of Crohn disease, but how this mutation influences the function of ATG16L1 has remained unclear. In a recent report, we showed that the A300 allele alters the ability of the C-terminal WD40 domain of ATG16L1 to interact with p...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1216303

    authors: Serramito-Gómez I,Boada-Romero E,Pimentel-Muiños FX

    更新日期:2016-11-01 00:00:00

  • PARK7 modulates autophagic proteolysis through binding to the N-terminally arginylated form of the molecular chaperone HSPA5.

    abstract::Macroautophagy is induced under various stresses to remove cytotoxic materials, including misfolded proteins and their aggregates. These protein cargoes are collected by specific autophagic receptors such as SQSTM1/p62 (sequestosome 1) and delivered to phagophores for lysosomal degradation. To date, little is known ab...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2018.1491212

    authors: Lee DH,Kim D,Kim ST,Jeong S,Kim JL,Shim SM,Heo AJ,Song X,Guo ZS,Bartlett DL,Oh SC,Lee J,Saito Y,Kim BY,Kwon YT,Lee YJ

    更新日期:2018-01-01 00:00:00