Exosomes exert cardioprotection in dystrophin-deficient cardiomyocytes via ERK1/2-p38/MAPK signaling

Gartz, Melanie; Darlington, Ashley; Afzal, Muhammed Zeeshan; Strande, Jennifer L.

doi:10.1038/s41598-018-34879-6

Cited by 38 publications

(36 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although detailed mechanisms of their anti-apoptotic effects are not fully deciphered, exosomes from iPSC-CMs has been shown to possess a powerful cardiac protective effect by preserving the mitochondrial membrane potential, decreasing the translocation of Bax to the mitochondria, delaying the mPTP opening time, and inhibiting caspase 3/7 protein activity under (hypoxic/ischemic) conditions [need citations]. These cardiac protective effects depend on the ERK1/2 and p38-MAPK signal pathway (Gartz et al, 2018). It has been found that programmed cell death 6 interacting protein, also known as Apoptosis-linked gene 2-interacting protein X (ALIX), is an endosomal sorting complex required for transport complex-associated protein.…”

Section: Anti-apoptotic Effects Of Ipsc Exosomesmentioning

confidence: 99%

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Fan

Zhang

Joshi

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.

show abstract

Section: Anti-apoptotic Effects Of Ipsc Exosomesmentioning

confidence: 99%

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Fan

Zhang

Joshi

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Given the 24 h period of SC-EV exposure to myotubes there is ostensibly sufficient duration to allow translation of delivered RNA or incorporation of delivered protein into the appropriate cellular compartments, including the mitochondria, themselves. Gartz et al (2019) demonstrated that exosomes from wild type and dystrophin-deficient induced pluripotent stem cellderived cardiomyocytes exert cardioprotective effects on dystrophic cardiomyocytes [44]. The authors attributed these findings to a decrease in reactive oxygen species and delay in the formation of the mitochondrial transition pore following oxidative injury with H 2 O 2 , mediated by ERK1/2 and p38 MAPK signaling.…”

Section: Discussionmentioning

confidence: 99%

Satellite cell-derived extracellular vesicles reverse peroxide-induced mitochondrial dysfunction in myotubes

Shuler

Wilson

Muñoz

et al. 2020

Preprint

View full text Add to dashboard Cite

3 ABSTRACTSatellite cells (SCs) are muscle-specific stem cells that have a central role in muscle remodeling. Despite their therapeutic potential, SC-based therapies have been met with numerous logistical challenges, limiting their ability to effectively treat systemic muscle diseases, such as Duchenne muscular dystrophy (DMD). Delivery of SC-derived extracellular vesicles (SC-EVs) may unlock the potential offered by SCs and overcome their numerous limitations. Purpose: The purpose of this investigation was to determine the extent to which SC-EVs could restore mitochondrial function in cultured myotubes following oxidative injury. Methods: SC-EVs were isolated from cultured SCs from C57 mice and quantified using nanoparticle tracking analysis (NTA). C2C12 myotubes were cultured and divided into four treatment groups: untreated control, treated for 24 h with SC-EV, 24 h exposure to 50 μ M H 2 O 2 followed by a 24 h recovery period with no treatment, or 24 h exposure to 50 μ M H 2 O 2 followed by a 24 h treatment with SC-EV. Inter-group differences in mitochondrial function were assessed via one-way ANOVA with Tukey post hoc analysis (p<0.05). Results: Given the seeding density used, we calculated that each SC releases approximately 2.35 x 10 5 ± 3.10 x 10 4 EVs per 24 h. Further, using fluorescent microscopy, we verified SC-EVs deliver cargo into myotubes, some of which was localized to the mitochondria. H 2 O 2 exposure resulted in a 42% decline in peak mitochondrial respiration (p=0.0243) as well as a 46% reduction in spare respiratory capacity (p=0.0185) relative to the untreated control group. Subsequent treatment with SC-EVs (3.12x10 8 SC-EV; 24 h) following H 2 O 2 exposure restored 76% of peak mitochondrial respiration (p=0.0187) and 84% of spare respiratory capacity in the damaged myotubes (p=0.0198). SC-EVs did not affect mitochondrial function in the undamaged myotubes. Conclusion: Collectively, these data demonstrate SC-EVs may represent a novel therapeutic approach for treatment of myopathies associated with mitochondrial dysfunction.

show abstract

“…Additionally, the pro-hypertrophic, pro-survival and pro-death effects of ERK1/2 converge on mitochondria upon their crucial roles in metabolism of cardiomyocyte. In response to types of stimuli, ERK1/2 can modulate mitochondria-mediated cardiomyocyte function directly through the interaction with mitochondria [24], or indirectly, by activation/inhibition of ERK-dependent downstream signaling molecules or mediators [25][26][27][28].…”

Section: Components and Regulation Of The Erk Cascadementioning

confidence: 99%

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

Yan

Zeng

et al. 2021

Cardiol J.

View full text Add to dashboard Cite

Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2(ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPKKs, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.

show abstract

Exosomes exert cardioprotection in dystrophin-deficient cardiomyocytes via ERK1/2-p38/MAPK signaling

Cited by 38 publications

References 47 publications

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Satellite cell-derived extracellular vesicles reverse peroxide-induced mitochondrial dysfunction in myotubes

Role of extracellular signal-regulated kinase 1/2 signaling underlying cardiac hypertrophy

Contact Info

Product

Resources

About