Mef2c Regulates Transcription of the Extracellular Matrix Protein Cartilage Link Protein 1 in the Developing Murine Heart

Lockhart, Marie; Wirrig, Elaine E.; Phelps, Aimee L.; Ghatnekar, Angela V.; Barth, Jeremy L.; Norris, Russell A.; Wessels, Andy

doi:10.1371/journal.pone.0057073

Cited by 22 publications

(21 citation statements)

References 34 publications

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“…Sox9 is required for chondrogenesis, 18 and for the expression of Hyaluronan and Proteoglycan Link protein 1 (Hapln1) in developing heart valves. 32, 33 Hapln1 is normally restricted to the ventricularis side of Cre-negative control AoVs (Fig. 3A, C), but its expression is expanded throughout the proteoglycan-rich nodules in PostnCre;Ctnnb1 fl/fl AoVs, as detected by immunofluorescent staining (Fig.…”

Section: Resultsmentioning

confidence: 91%

Loss of β-Catenin Promotes Chondrogenic Differentiation of Aortic Valve Interstitial Cells

Fang

Alfieri

Hulin

et al. 2014

ATVB

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Objective The Wnt/β-catenin signaling pathway has been implicated in human heart valve disease and is required for early heart valve formation in mouse and zebrafish. However, the specific functions of Wnt/β-catenin signaling activity in heart valve maturation and maintenance in adults have not been previously determined. Approach and Results Here, we show that Wnt/β-catenin signaling inhibits Sox9 nuclear localization and proteoglycan expression in cultured chicken embryo aortic valves (AoVs). Loss of β-catenin in vivo in mice, using Periostin(Postn)Cre-mediated tissue-restricted loss of β-catenin (Ctnnb1) in valvular interstitial cells (VICs), leads to the formation of aberrant chondrogenic nodules and induction of chondrogenic gene expression in adult AoVs. These nodular cells strongly express nuclear Sox9, and Sox9 downstream chondrogenic extracellular matrix (ECM) genes, including Aggrecan, Col2a1, and Col10a1. Excessive chondrogenic proteoglycan accumulation and disruption of stratified ECM maintenance in the AoV leaflets are characteristics of myxomatous valve disease. Both in vitro and in vivo data demonstrate that loss of Wnt/β-catenin signaling leads to increased nuclear expression of Sox9 concomitant with induced expression of chondrogenic ECM proteins. Conclusions β-catenin limits Sox9 nuclear localization and inhibits chondrogenic differentiation during valve development and in adult AoV homeostasis.

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Section: Resultsmentioning

confidence: 91%

Loss of β-Catenin Promotes Chondrogenic Differentiation of Aortic Valve Interstitial Cells

Fang

Alfieri

Hulin

et al. 2014

ATVB

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“…These two networks suggested the potential associations between cir-cRNAs and their target genes. 40 However, we only compared the circRNA expression in 40 pairs of patients. 37 In this study, we predicted the interaction of circRNA/miRNA and the target genes related to CHD.…”

Section: Discussionmentioning

confidence: 99%

“…39 Mef2c could regulate the expression of cardiac extracellular matrix protein. 40 However, we only compared the circRNA expression in 40 pairs of patients. The cohort is not large enough to get a definite conclusion.…”

Section: Discussionmentioning

confidence: 99%

Circulating plasma circular RNAs as novel diagnostic biomarkers for congenital heart disease in children

Liu

et al. 2019

Clinical Laboratory Analysis

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ObjectiveThe diagnostic value of circulating circular RNAs (circRNAs) has received more and more attention. However, little has been reported about their potential in the diagnosis of congenital heart diseases (CHD). In this study, we explored differential expression of circRNAs from children with CHD to evaluate their potential as clinical biomarkers.MethodsWe established a discovery cohort (four CHD cases; four matched healthy controls) and a validation cohort (40 CHD cases; 40 matched healthy controls). Microarray expression analysis was performed on the discovery set to identify candidate circRNAs. Candidates were further validated in the validation set. The diagnostic accuracy of circRNAs was determined by receiver operating characteristic (ROC) analysis. Gene ontology (GO), pathway, and network analysis were performed to predict a network of circRNA/miRNA and target mRNAs related to CHD.ResultsThe top seven significantly differentially expressed CHD‐associated circRNAs were validated by RT‐PCR as follows: hsa_circRNA_004183, hsa_circRNA_079265, hsa_circRNA_105039, hsa_circRNA_404686, hsa_circRNA_101050, hsa_circRNA_100787, and hsa_circRNA_101328. Three significantly down‐regulated circRNAs (hsa_circRNA_004183, hsa_circRNA_079265, and hsa_circRNA_105039) were identified with area under curve (AUC) values of 0.758, 0.809, and 0.907, respectively; the combination had an AUC of 0.965. An interaction network was constructed by 43 circRNAs, 9 miRNAs, and 29 mRNAs, which involved in heart development.ConclusionsWe identified three circRNAs under‐expressed in plasma from children with CHD. These circRNAs may be crucial in the development of CHD and may serve as novel non‐invasive biomarkers for the diagnosis of CHD in children.

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“…(b)]. This gene plays a key role in myogenesis and has long been associated with the regulation of myocardial‐expressed genes . The expression of GATA4 and NKX2.5 , also early cardiac markers, was not detected, which was not surprising at this early time point considering that at least 1 to 4 weeks have been reported to be needed for implanted mesenchymal stem cells to reach differentiation into cardiomyocytes within heart .…”

Section: Resultsmentioning

confidence: 94%

in vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue‐derived progenitor cells

Castells-Sala

Martínez‐Ramos

Vallés-Lluch

et al. 2015

J Biomedical Materials Res

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WileyCastells-Sala, C.; Martínez Ramos, C.; Vallés Lluch, A.; Monleón Pradas, M.; Semino, C. (2015). In vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue-derived progenitor cells. platform. Specifically, here we tested the effect of the RAD16-I peptide gel in microporous poly(ethyl acrylate) polymers (PEA) using two-dimensional PEA films as controls. Results showed optimal cell adhesion efficiency and growth in the polymers coated with the self-assembling peptide RAD16-I. Importantly, subATDPCs seeded into microporous PEA scaffolds coated with RAD16-I maintained its phenotype by assessing specific progenitor markers using protein and gene expression analysis. These data suggest that this bioimplant (scaffold/RAD16-I/cells) can be suitable for further in vivo implantation with the aim to improve the function of affected tissue after myocardial infarction.

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Mef2c Regulates Transcription of the Extracellular Matrix Protein Cartilage Link Protein 1 in the Developing Murine Heart

Cited by 22 publications

References 34 publications

Loss of β-Catenin Promotes Chondrogenic Differentiation of Aortic Valve Interstitial Cells

Loss of β-Catenin Promotes Chondrogenic Differentiation of Aortic Valve Interstitial Cells

Circulating plasma circular RNAs as novel diagnostic biomarkers for congenital heart disease in children

in vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue‐derived progenitor cells

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