Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats

Gao

Cell Biology International

et al. 2021

microRNAs (miRNAs) are of importance to chronic heart failure (CHF). However, the relevance of the exosomal miRNAs produced during CHF remains unknown. Our purpose here was to examine the relevance of exosomal microRNA‐1246 (miR‐1246) released from human umbilical cord mesenchymal stem cell (hucMSC) during CHF and the mechanism of action. Cardiac function, myocardial infarction area, apoptosis, and angiogenesis were all evaluated in a CHF rat model following treatment with hucMSC‐derived exosomes (hucMSC‐Exos). H9C2 and human umbilical vascular endothelial cells (HUVECs) were subjected to oxygen and glucose deprivation and exosome treatment to quantify the cell proliferation and apoptosis in H9C2 cells and the tube formation capacity of the HUVECs. A dual‐luciferase activity reporter assay was conducted to validate the interaction between miR‐1246 and serine protease 23 (PRSS23). HucMSCs treatment led to a reduction in H9C2 apoptosis and an increase in HUVEC angiogenesis, which were mitigated when hucMSCs were treated with a miR‐1246 inhibitor. We also confirmed that PRSS23 is a putative target of miR‐1246 and that miR‐1246 attenuated hypoxia‐induced myocardial tissue damage by targeting PRSS23 and inhibiting the activation of the Snail/alpha‐smooth muscle actin signaling. Our findings suggest that exosomal miR‐1246 from hucMSCs protects the heart from failure by targeting PRSS23.

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA‐1246 from human umbilical cord mesenchymal stem cells potentiates myocardial angiogenesis in chronic heart failure

Gao

Cell Biology International

et al. 2021

Environmental Toxicology

“…The accelerated re‐endothelialization of the damaged vessels may be important for the recovery of endothelial function and promote angiogenesis 33 . It has been demonstrated that activation of ERK1/2 signal pathway accelerated the re‐endothelialization 34 . In recent years, the fact that activation of the MEK/ERK signal pathway can promote angiogenesis and cancer cell proliferation during tumor development has been evidenced by a lot of empirical researches.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect and molecular mechanism of Salvia Miltiorrhiza on rats with acute brain injury after carbon monoxide poisoning based on the strategy of internet pharmacology

Yue

et al. 2021

The pathogenesis of brain injury caused by carbon monoxide poisoning (COP) is very complex, and there is no exact and reliable treatment in clinic. In the present study, we screened the therapeutic target and related signal pathway of Salvia Miltiorrhiza for acute COP brain injury, and clarified the pharmacological mechanism of multicomponent, multitarget, and multisignal pathway in Salvia Miltiorrhiza by network pharmacology. To further verify the therapeutic effect of Salvia Miltiorrhiza on acute brain injury based on the results of network analysis, a total of 216 male healthy Sprague Dawley rats were collected in the present study and randomly assigned to a normal control group, a COP group and a Tanshinone IIA sulfonate treatment group (72 rats in each group). The rat model of acute severe COP was established by the secondary inhalation in a hyperbaric oxygen chamber. We found that Salvia Miltiorrhiza had multiple active components, and played a role in treating acute brain injury induced by COP through multiple targets and multiple pathways, among them, MAPK/ERK1/2 signaling pathway was one of the most important. COP can start apoptosis process, activate the MAPK/ERK1/2 signaling pathway, and promote the expression of VEGF‐A protein and the formation of brain edema. Tanshinone IIA can effectively inhibit apoptosis, up‐regulate the expressions of VEGF‐A, P‐MEK1/2 and P‐ERK1/2 proteins, thereby protect endothelial cells, promote angiogenesis and microcirculation, and finally alleviate brain edema.

“…Studies have been focused on modulating the culture microenvironments of EVs-secreting donor cells, such as altering ingredients, oxidative stress, and physical cues. Specifically, EVs have been generated under different conditions, involving differentiation medium, 30 , 31 hypoxia, 32 , 33 3D culture, 34 mechanical force, 35 , 63 and their combinations (e.g. 3D culture + mechanical force).…”

Section: Payload Content and Bioactivity Of Evsmentioning

confidence: 99%

Emerging biogenesis technologies of extracellular vesicles for tissue regenerative therapeutics

et al. 2021

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.