Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction

Gao, Feng; Kataoka, Masaharu; Liu, Ning; Liang, Tian; Huang, Zhan-Peng; Gu, Fei; Ding, Jianping; Liu, Jianming; Zhang, Feng; Ma, Qing; Wang, Yingchao; Zhang, Mingming; Hu, Xiaoyun; Kyselovič, Ján; Hu, Xinyang; Pu, William T.; Wang, Jianan; Chen, Jinghai; Wang, Da Zhi

doi:10.1038/s41467-019-09530-1

Cited by 198 publications

(151 citation statements)

References 41 publications

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“…20) MiR-19a/19b could reduce MI-induced cardiac damage and protect cardiac function. 21) Despite the therapies of miRNAs in MI, there are still many miRNAs that act as a potential therapeutic target in MI. MiR-221-3 p serves as a novel marker for early prediction of AMI.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

et al. 2020

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Myocardial infarction (MI) is one of the major causes of death worldwide, and the therapeutic strategies of MI are still limited. In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/ R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modulation of miR-665 may have the potential to counteract the development of MI.

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Section: Discussionmentioning

confidence: 99%

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

et al. 2020

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“…Previous studies have reported that the expression of miR-19 was increased in response to the stimulation including infarction or infection. 21,22 Therefore, further research is required to produce a clear conclusion on the protective effects of miR-19b on AC. A higher number of experimental samples and additional time points can be used in future studies.…”

Section: Discussionmentioning

confidence: 99%

The Potential Inhibitory Effects of miR-19b on Ocular Inflammation are Mediated Upstream of the JAK/STAT Pathway in a Murine Model of Allergic Conjunctivitis

Guo

Liu

Peng

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Guo C, Liu J, Hao P, et al. The potential inhibitory effects of miR-19b on ocular inflammation are mediated upstream of the JAK/STAT pathway in a murine model of allergic conjunctivitis. Invest Ophthalmol Vis Sci. 2020;61(3):8. https://doi.org/10.1167/iovs.61.3.8 PURPOSE.Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine that initiates allergic inflammatory reaction between epithelial and dendritic cells (DCs). miR-19b was reported to suppress TSLP expression. The present study aimed to examine miR-19b expression, regulation, and function in allergic conjunctivitis (AC). METHODS.A murine model of experimental AC was induced in BALB/c mice by short ragweed pollen. The serum, eye balls, conjunctiva, and cervical lymph nodes (CLN) were used for the study. Gene expression was determined by RT-PCR, whereas protein production and activation were evaluated by immunostaining, ELISA, and Western blotting. RESULTS.In the murine AC model, miR-19b was aberrantly downregulated, whereas the levels of TSLP and p-STAT3, as well as the number of CD11c+ pSTAT3+ DCs were increased. Moreover, Th2 inflammatory cytokine expression was significantly increased. These severe phenotypes could be counteracted by either applying exogenous miR-19b mimic microRNAs or the JAK/STAT inhibitor CYT387. Moreover, overexpression of miR-19b repressed p-STAT3 expression and the number of CD11c+ cells in AC eye and CLN tissues.CONCLUSIONS. These findings suggested that miR-19b reduced ocular surface inflammation by inhibiting Stat3 signaling via TSLP downregulation in a murine AC model. Moreover, the present study further demonstrated the clinical potential of applying miR-19b and anti-JAK/STAT therapies in the treatment of AC.

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“…Here we refer to heart-specific microRNAs known together as myomiRs (myo = muscle + miR = microRNA), such as mir-128, miR-19a/19b, and other miRNAs with known effects on the heart. They were recently found to play a role in pivotal cell functions involved in cardiac regeneration, i.e., proliferation, reprogramming and differentiation (Huang et al, 2018;Gao et al, 2019).…”

Section: Endogenous Cardiomyocytes Proliferation Induction Mirna Regumentioning

confidence: 99%

“…Cardiac protection-mediated expression induced in heart failure (Gao et al, 2019) Enhancement of cardiomyocytes proliferation in response to cardiac injury (Gao et al, 2019) mir-138 hsa-mir-138-1 hsa-mir-138-2 hsa-miR-138-5p hsa-miR-138-5p…”

Section: Growth Factorsmentioning

confidence: 99%

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

Cassani

Fernandes

Vrbský

et al. 2020

Front. Bioeng. Biotechnol.

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Cassani et al. Nanoparticles for Heart Regeneration function are some of the main achievements reached so far by nanoparticle-based treatments in animal models. This work offers an overview on the recent nanomedical applications for cardiac regeneration and highlights how the versatility of nanomaterials can be combined with the newest molecular biology discoveries to advance cardiac regeneration therapies.

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Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction

Cited by 198 publications

References 41 publications

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

The Potential Inhibitory Effects of miR-19b on Ocular Inflammation are Mediated Upstream of the JAK/STAT Pathway in a Murine Model of Allergic Conjunctivitis

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

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