miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon acute drug-induced cardiac injury in rats

Gryshkova, Vitalina; Fleming, Alisha; McGhan, Portia; Ron, Pierrette De; Fleurance, Renaud; Valentin, Jean‐Pierre; Costa, André Nogueira da

doi:10.1016/j.toxlet.2018.01.013

Cited by 23 publications

(17 citation statements)

References 58 publications

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“…Leukocytes and platelets are major contributors to the tissue injury response ( 45 ). Thus, the widely reported induction of miR-21 upon injury may be secondary to an immune cell infiltration or platelet deposition rather than induction of miR-21 expression in resident cells ( 46 ). In addition, expression and processing of the miR-21 precursor is enhanced by TGF-β signaling ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of profibrotic microRNA-21 affects platelets and their releasate

Barwari¹,

Eminaga²,

Mayr³

et al. 2018

JCI Insight

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Fibrosis is a major contributor to organ disease for which no specific therapy is available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how miR-21 inhibition may attenuate fibrosis using a proteomics approach. Transfection of miR-21 mimic or inhibitor in murine cardiac fibroblasts revealed limited effects on extracellular matrix (ECM) protein secretion. Similarly, miR-21–null mouse hearts showed an unaltered ECM composition. Thus, we searched for additional explanations as to how miR-21 might regulate fibrosis. In plasma samples from the community-based Bruneck Study, we found a marked correlation of miR-21 levels with several platelet-derived profibrotic factors, including TGF-β1. Pharmacological miR-21 inhibition with an antagomiR reduced the platelet release of TGF-β1 in mice. Mechanistically, Wiskott-Aldrich syndrome protein, a negative regulator of platelet TGF-β1 secretion, was identified as a direct target of miR-21. miR-21–null mice had lower platelet and leukocyte counts compared with littermate controls but higher megakaryocyte numbers in the bone marrow. Thus, to our knowledge this study reports a previously unrecognized effect of miR-21 inhibition on platelets. The effect of antagomiR-21 treatment on platelet TGF-β1 release, in particular, may contribute to the antifibrotic effects of miR-21 inhibitors.

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Section: Discussionmentioning

confidence: 99%

Inhibition of profibrotic microRNA-21 affects platelets and their releasate

Barwari¹,

Eminaga²,

Mayr³

et al. 2018

JCI Insight

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“…A previous study showed that miR-21-5p relieves leakage from damaged brain microvascular endothelial barrier by inhibiting inflammation and apoptosis [48]. MiR-21-5p is a potential biomarker of cardiac inflammatory infiltration during acute drug-induced cardiac injuries [24], and is up-regulated in type 1 diabetes by the action of inflammatory cytokines [49]. In our study, we found that PGE1 up-regulated miR-21-5p expression in rat cardiomyocytes under conditions of H/R injury, and inhibited the apoptosis ability of rat cardiomyocytes by up-regulating miR-21-5p.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal miRNA expression can lead to myocardial reperfusion injuries [21][22][23]. Studies have indicated that miR-21-5p plays essential roles in acute drug-induced cardiac injuries [24] in hyperlipidemia rats [25] and high glucose-induced retinal microvascular endothelial cells [26]. Therefore, it is extremely important to study the mechanism and function of miR-21-5p in rat cardiomyocytes being exposed to conditions of H/R.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

et al. 2019

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Background: Prostaglandin-E1 (PGE1) is a potent vasodilator with anti-inflammatory and antiplatelet effects. However, the mechanism by which PGE1 contributes to the amelioration of cardiac injury remains unclear. Methods: The present study was designed to investigate how PGE1 protects against hypoxia/reoxygenation (H/R)-induced injuries by regulating microRNA-21-5p (miR-21-5p) and fas ligand (FASLG). Rat H9C2 cells and isolated primary cardiomyocytes were cultured under hypoxic conditions for 6 h (6H, hypoxia for 6 h), and reoxygenated for periods of 6 (6R, reoxygenation for 6 h), 12, and 24 h, respectively. Cells from the 6H/6R group were treated with various doses of PGE1; after which, their levels of viability and apoptosis were detected. Results: The 6H/6R treatment regimen induced the maximum level of H9C2 cell apoptosis, which was accompanied by the highest levels of Bcl-2-associated X protein (Bax) and cleaved-caspase-3 expression and the lowest level of B-cell lymphoma 2 (Bcl-2) expression. Treatment with PGE1 significantly diminished the cell cytotoxicity and apoptosis induced by the 6H/6R regimen, and also decreased expression of IL-2, IL-6, P-p65, TNF-α, and cleaved-caspase-3. In addition, we proved that PGE1 up-regulated miR-21-5p expression in rat cardiomyocytes exposed to conditions that produce H/R injury. FASLG was a direct target of miR-21-5p, and PGE1 reduced the ability of H/R-injured rat cardiomyocytes to undergo apoptosis by affecting the miR-21-5p/FASLG axis. In addition, we proved that PGE1 could protect primary cardiomyocytes against H/R-induced injuries. Conclusions: These results indicate that PGE1 exerts cardioprotective effects in H9C2 cells during H/R by regulating the miR-21-5p/FASLG axis.

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“…Beta-blocker use correlates with better overall survival in metastatic MM, protects patients from disease recurrence and improves the efficacy of immunotherapies in mice [ 354 , 355 , 356 ]. Catecholamine stimulation of B 1-2 -AR via activation of STAT3 upregulates miR-21 expression [ 357 , 358 , 359 , 360 , 361 , 362 , 363 , 364 ], whereas beta-blocker treatment attenuates miR-21 expression [ 364 ]. Beta-blocker-mediated reduction of miR-21 expression may also explain their anti-angiogenic effects in infantile hemangioma [ 365 ].…”

Section: Therapeutic Suppression Of Mir-21mentioning

confidence: 99%

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

Melnik

John

Carrera-Bastos

et al. 2020

Cancers

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DNA mutation-induced activation of RAS-BRAF-MEK-ERK signaling associated with intermittent or chronic ultraviolet (UV) irradiation cannot exclusively explain the excessive increase of malignant melanoma (MM) incidence since the 1950s. Malignant conversion of a melanocyte to an MM cell and metastatic MM is associated with a steady increase in microRNA-21 (miR-21). At the epigenetic level, miR-21 inhibits key tumor suppressors of the RAS-BRAF signaling pathway enhancing proliferation and MM progression. Increased MM cell levels of miR-21 either result from endogenous upregulation of melanocytic miR-21 expression or by uptake of miR-21-enriched exogenous exosomes. Based on epidemiological data and translational evidence, this review provides deeper insights into environmentally and metabolically induced exosomal miR-21 trafficking beyond UV-irradiation in melanomagenesis and MM progression. Sources of miR-21-enriched exosomes include UV-irradiated keratinocytes, adipocyte-derived exosomes in obesity, airway epithelium-derived exosomes generated by smoking and pollution, diet-related exosomes and inflammation-induced exosomes, which may synergistically increase the exosomal miR-21 burden of the melanocyte, the transformed MM cell and its tumor environment. Several therapeutic agents that suppress MM cell growth and proliferation attenuate miR-21 expression. These include miR-21 antagonists, metformin, kinase inhibitors, beta-blockers, vitamin D, and plant-derived bioactive compounds, which may represent new options for the prevention and treatment of MM.

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miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon acute drug-induced cardiac injury in rats

Cited by 23 publications

References 58 publications

Inhibition of profibrotic microRNA-21 affects platelets and their releasate

Inhibition of profibrotic microRNA-21 affects platelets and their releasate

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

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