Critical roles of miRNA-mediated regulation of TGF  signalling during mouse cardiogenesis

Peng, Yin; Song, Lanying; Zhao, Ming; Harmelink, Cristina; DeBenedittis, Paige; Cui, Xiangqin; Wang, Qin; Jiao, Kai

doi:10.1093/cvr/cvu126

Cited by 27 publications

(37 citation statements)

References 63 publications

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“…Endothelial cell (EC) injury and inflammation have been largely implicated in the formation of coronary atherosclerosis [5, 6]. It is also well-established that microRNAs (miRNAs) participate in pathological processes in the cardiovascular system, such as endothelial dysfunction, inflammation, apoptosis, angiogenesis, and atherosclerosis [7, 8]. Therefore, it is possible that miRNAs may have a potential relationship with EC injury and inflammation in CHD.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study aimed to identify the role of microRNA-22 (miR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), miR-22 mimic, miR-22 inhibitor and miR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between miR-22 and NLRP3. MiR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased miR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the miR-22 mimic group and significantly reduced in the miR-22 inhibitor group. The miR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the miR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the miR-22 mimic group. In contrast, in the miR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that miR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Huang

Wei

Lin

et al. 2017

Cell Physiol Biochem

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“…Mutant hearts showed an upregulation of a dozen contractile proteins such as actinin, cTnC, MHC[s3], myosin light chain [s4](MLC)1V and MLC2V, as well as an increase in transforming growth factor β receptor (TGFBR)1 activity. By contrast, blocking TGFBR1 activity partially rescues the heart from defects caused by the inactivation of Dicer in vivo [21]. Specifically, myocardial inactivation of Dicer under the control of a promoter for the cardiomyocyte structural protein alpha myosin heavy chain (αMHC) in mice resulted in dilated cardiomyopathy, heart failure and postnatal lethality, which was consistent with the disruption in expression of cardiac contractile proteins, as well as changes in sarcomeric structure [22].…”

Section: Mechanisms Of Mirnas In the Regulation Of Normal Cardiovascumentioning

confidence: 99%

“…Recently, Peng [s2] et al . demonstrated that specifically inactivating Dicer in the myocardium by crossing cTnt-Cre mice with Dicer loxP mice efficiently inactivated target genes in cardiomyocytes at mid-gestation, thus leading to severe myocardial wall defects, including reduced cell proliferation, increased cell death and spongy myocardial wall, and ultimately resulting in the death of all mutants between E14.5 and E16.5 [21]. Mutant hearts showed an upregulation of a dozen contractile proteins such as actinin, cTnC, MHC[s3], myosin light chain [s4](MLC)1V and MLC2V, as well as an increase in transforming growth factor β receptor (TGFBR)1 activity.…”

Section: Mechanisms Of Mirnas In the Regulation Of Normal Cardiovascumentioning

confidence: 99%

Mechanisms and therapeutic potential of microRNAs in hypertension

Shi

Liao

Liu

et al. 2015

Drug Discovery Today

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Hypertension is the major risk factor for the development of stroke, coronary artery disease, heart failure and renal disease. The underlying cellular and molecular mechanisms of hypertension are complex and remain largely elusive. MicroRNAs (miRNAs) are short, noncoding RNA fragments of 22–26 nucleotides and regulate protein expression post-transcriptionally by targeting the 3′-untranslated region of mRNA. A growing body of recent research indicates that miRNAs are important in the pathogenesis of arterial hypertension. Herein, we summarize the current knowledge regarding the mechanisms of miRNAs in cardiovascular remodeling, focusing specifically on hypertension. We also review recent progress of the miRNA-based therapeutics including pharmacological and nonpharmacological therapies (such as exercise training) and their potential applications in the management of hypertension.

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“…Available data have suggested that miRNAs target genes that regulate neurulation and cardiogenesis, including transcription factors and genes in growth factor signaling (e.g., the TGFβ and Wnt families) [36; 40; 48; 49]. …”

Section: Micrornas As Biomarkers For Detection Of Embryonic Malformatmentioning

confidence: 99%

MicroRNA Biomarkers for Early Detection of Embryonic Malformations in Pregnancy

Zhao

2014

J Biomol Res Ther

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Congenital birth defects, manifested in newborn infants, are formed during early embryogenesis. Targeted and individualized interventions to prevent birth defects require early detection of risk and signs of developmental abnormalities. Current diagnosis of structural anomalies largely relies on ultrasonography, which can only detect abnormities after their formation in fetuses. Biomolecules, mainly proteins, in maternal blood have been used as indicators of fetal anomalies; however, they lack adequate sensitivity for detecting embryonic malformations. Recently, cell-free microRNAs (miRNAs) have been found in blood and evaluated as biomarkers for diseases. Expression of certain miRNAs in maternal plasma has been shown to be correlated with birth defects in infants. Although their reliability and sensitivity remain to be validated, miRNAs, which can be amplified and sequenced, are potentially sensitive and specific biomarkers for early embryonic dysmorphogenesis.

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Critical roles of miRNA-mediated regulation of TGF signalling during mouse cardiogenesis

Cited by 27 publications

References 63 publications

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Mechanisms and therapeutic potential of microRNAs in hypertension

MicroRNA Biomarkers for Early Detection of Embryonic Malformations in Pregnancy

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