MiR-29b Inhibits Ventricular Remodeling By Activating Notch Signaling Pathway in the Rat Myocardial Infarction Model

Background: To study the effect of miR-29b on myocardial infarction via Notch signaling pathway in rats. Methods: The rat acute myocardial infarction (AMI) models were established and were divided into AMI group, sham group and normal group (N = 10 in each group). HE (Hemotoxylin and eosin) staining was used to detect whether the model was constructed successfully. MiR-29b mimics, inhibitors, mimics negative control (NC) were transfected into H9c2 (2-1) cells. Then, cells were divided into a mimics group, inhibitor group, NC group, and blank group. The relative expression levels of miR-29b, Notch1, DII4 and Hesl were detected by qRT-PCR. The expression of NICD1 was detected by Western blotting. Results: The rat AMI model was successfully constructed. Compared with normal and sham groups, the miR-29b expression was down-regulated, while the expression of Notch1, DII4 and Hesl was increased, and the NICD1 protein expression was increased in the myocardial infarction area of the AMI group (P < .05). Compared with the NC and blank groups, the relative expression of Notch1, DII4, Hesl and NICD1 were upregulated in the mimics group (P < .05), whereas the expression of Notch1, DII4, Hesl and NICD1 in the inhibitor group was decreased (P < .05). Conclusion: MiR-29b inhibited myocardial fibrosis and cardiac hypertrophy by activating the Notch signaling pathway and protected myocardium against myocardial infarction.

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Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.639476 ◽

2022 ◽

Vol 8 ◽

Author(s):

Zhi Li ◽

Miao Nie ◽

Liming Yu ◽

Dengshun Tao ◽

Qiang Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Notch Signaling ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Macrophage Polarization ◽

Notch Signaling Pathway ◽

Inflammatory Factors ◽

M2 Macrophage ◽

M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

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Treatment of Intrauterine Adhesions with Human Amnion Mesenchymal Stromal Cells (hAMSCs) on Promoting Endometrial Regeneration and Repair Via Notch Signaling Pathway Regulation

10.21203/rs.3.rs-92874/v1 ◽

2020 ◽

Author(s):

Jie Yu ◽

Wenwen Zhang ◽

Jiayue Huang ◽

Yating Gou ◽

Congcong Sun ◽

...

Keyword(s):

Epithelial Cells ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Intrauterine Adhesions ◽

Epithelial Markers ◽

Qrt Pcr ◽

Endometrial Epithelial Cells

Abstract Background: Human amniotic mesenchymal stem cells(hAMSCs) can repair and improve the damaged endometrium which its aplastic disorder is the main reason for intrauterine adhesions(IUAs).Methods: We conducted in vivo and in vitro experiments. In vivo experiments: 45 female Sprague-Dawley(SD) rats were involved and randomized equally into Sham group, IUA group, Estradiol(E2) group, hAMSCs group, and E2 + hAMSCs group. The effect of hAMSCs and E2 only or combined was evaluated by Hematoxylin-eosin(HE) and Masson staining. The expression of epithelial markers and key proteins of Notch signaling pathway by Immunohistochemistry. In vitro experiments: Firstly, the hAMSCs cells were taken and divided into control group and induced group in which hAMSCs were differentiated into endometrial epithelial cells in induced microenvironment, and extracted their RNA respectively. The expression of epithelial markers and Notch1 messenger RNA (mRNA) was detected by Real-time quantitative polymerase chain reaction(qRT-PCR). and the changes in expression position of Notch intracellular domain(NICD) and expression amount of target gene, hairy enhancer of split 1(Hes1) were detected by Immunofluorescence. Then, Activated and inhibited the Notch signaling pathway while induction, and detected mRNA expression of hAMSCs epithelial markers by quantitative real-time polymerase chainreaction (qRT-PCR) respectively and detected hAMSCs cell cycle by flow cytometric. Results:This study showed that hAMSCs alone or combined with E2 could promote endometrial repair, and Notch signaling pathway a great role in it. And otherwise, the activation or habitation of Notch signaling pathway determines whether hAMSCs could differentiate into endometrial epithelial cells or not.Conclusion: we concluded that activate the Notch signaling pathway promote the differentiation of hAMSCs into endometrial epithelial cells, and further treat IUAs.

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Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice

BioMed Research International ◽

10.1155/2018/5207031 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Yanru He ◽

Si Pang ◽

Jia Huang ◽

Kongbo Zhu ◽

Jiayi Tong ◽

...

Keyword(s):

Cardiac Function ◽

Notch Signaling ◽

Signaling Pathway ◽

Cardiac Remodeling ◽

Ventricular Remodeling ◽

Cardiac Injury ◽

Notch Signaling Pathway ◽

Protective Role ◽

Cardiomyocyte Apoptosis

Background. Ischemic heart disease (IHD) is the major cause of death in patients with cardiovascular disease. Cardiac remodeling is a common pathological change following myocardial infarction (MI), and cardiomyocyte apoptosis plays a key role in this change. Transcription factor recombination signal-binding protein-J (RBP-J)-mediated Notch signaling pathway has been implicated in several inherited cardiovascular diseases, including aortic valve diseases, but whether the RBP-J-mediated Notch signaling pathway plays a role in cardiomyocyte apoptosis after MI is unclear. Method. We crossed RBP-Jfl/fl mice and Myh6-Cre/Esr1 transgenic mice to delete RBP-J in vivo and to partly inhibit the canonical Notch signaling pathway. MI was induced in mice by permanent ligation of the left anterior descending coronary artery followed by the knockout of RBP-J. Cardiac function and morphology were assessed by echocardiography and histological analysis 4 weeks after infarction. In addition, the expression and regulation of apoptosis-related molecules were examined by real time PCR and western blot. Results. RBP-J knockout decreased the survival rate and deteriorated post-MI remodeling and function in mice, and this effect was associated with increased cardiomyocyte apoptosis. The potential mechanisms might be related to the downregulated expression of bcl-2, upregulated expression of bax, and cleaved-caspase 3 to exacerbate cardiomyocyte apoptosis. Conclusion. These findings show that the RBP-J-mediated Notch signaling pathway in cardiomyocytes limits ventricular remodeling and improves cardiac function after MI. The RBP-J-mediated Notch signaling pathway has a protective role in cardiomyocyte apoptosis following cardiac injury.

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Έκφραση του σηματοδοτικού μονοπατιού Notch σε πλακούντες εγκύων με προεκλαμψία

10.12681/eadd/35915 ◽

2015 ◽

Author(s):

Περσεφόνη Φραγκιαδάκη

Keyword(s):

Western Blot ◽

Notch Signaling ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Target Genes ◽

Notch Signaling Pathway ◽

Quantitative Real Time Pcr ◽

Notch 1 ◽

Qrt Pcr

Η προεκλαμψία αποτελεί μια από τις κυριότερες αιτίες μητρικής και εμβρυικής/νεογνικής νοσηρότητας και θνητότητας και επιπλέκει το 3-5% των κυήσεων. Προηγούμενες μελέτες έδειξαν ότι μέλη του σηματοδοτικού μονοπατιού Notch (Notch signaling pathway) εκφράζονται στον πλακούντα και παίζουν σημαντικό ρόλο στην ομαλή ανάπτυξη του ενεργοποιώντας μεταγραφικούς παράγοντες οι οποίοι αλλάζουν την έκφραση γονιδίων στόχων. Διαταραχές στη λειτουργία του μονοπατίου Notch σχετίζονται με παθολογική πλακουντοποίηση. Σκοπός της μελέτης αυτής είναι να εξετάσει την έκφραση των υποδοχέων (receptors) NOTCH1,-2,-3,-4, των συνδετών (ligands) DLL1,-3,-4, JAG1,-2 και των γονιδίων στόχων (target genes) HEY1,-2 σε πλακούντες κυήσεων με προεκλαμψία. Εξετάστηκαν δείγματα πλακουντιακού ιστού από 20 προεκλαμπτικές και από 20 φυσιολογικές κυήσεις. Τα επίπεδα mRNA των υπό εξέταση μορίων μετρήθηκαν με ποσοτική (quantitative) Real-Time PCR (qRT-PCR) ενώ η πρωτεϊνική έκφραση της ενδοκυττάριας περιοχής (intracellular domain) των NOTCH2 (NICD2) και NOTCH3 (NICD3) εκτιμήθηκαν με Western Blot (WB). Τα αποτελέσματα μας έδειξαν ότι οι υποδοχείς Notch-1 και Notch-4 αλλά και ο συνδέτης Dll-1 δεν εκφράζονται στους πλακούντες γυναικών με προεκλαμψία ή με φυσιολογική εγκυμοσύνη. Ωστόσο, τα επίπεδα έκφρασης mRNA των NOTCH2, NOTCH3, DLL3, DLL4, JAG1, JAG2, HEY1 and HEY2 ήταν μειωμένα στα παθολογικά δείγματα σε σχέση με τα φυσιολογικά (p<0.01). Η ανάλυση με WB επιβεβαίωσε ότι τα επίπεδα πρωτεϊνικής έκφρασης των NICD2 και NICD3 ήταν επίσης ελαττωμένα στα δείγματα της προεκλαμψίας (p=0.014 και p<0.001, αντίστοιχα). Περαιτέρω στατιστική ανάλυση έδειξε α) μη έκφραση σε γονιδιακό επίπεδο του υποδοχέα NOTCH3 στις εγκύους εκείνες που κάπνιζαν και στη διάρκεια της εγκυμοσύνης σε σχέση με εκείνες που το έκοψαν (p=0.029) και β) στις περιπτώσεις με προεκλαμψία και βάρος νεογνού μικρότερο από την 5η εκατοστιαία θέση παρατηρήσαμε υψηλότερα επίπεδα πρωτεΐνης του NICD-3 (p=0.028) και υψηλότερα επίπεδα mRNA του Dll-3 (p=0.041). Τα αποτελέσματα της μελέτης μας δείχνουν ότι το σηματοδοτικό μονοπάτι Notch αποτελεί σημαντικό μέρος της παθογένειας αυτής της επιπλοκής της εγκυμοσύνης. Περαιτέρω μελέτες απαιτούνται με σκοπό να διερευνηθεί βαθύτερα και να καθοριστεί ο ρόλος των εξετασθέντων μορίων στην προεκλαμψία και να μελετηθεί η δυνητική τους χρήση στην πρόβλεψη και τη διαγνωστική και θεραπευτική προσέγγιση της νόσου.

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Activation of the NOTCH signaling pathway stimulates migration of human b-lymphocytes

Pneumologie ◽

10.1055/s-0035-1551904 ◽

2015 ◽

Vol 69 (05) ◽

Author(s):

A Holzer ◽

K Watzinger ◽

CM Kähler

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

B Lymphocytes ◽

Notch Signaling Pathway

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The Role of miR-124 in Drosophila Alzheimer's Disease Model by Targeting Delta in Notch Signaling Pathway

Current Molecular Medicine ◽

10.2174/1566524016666151123114608 ◽

2015 ◽

Vol 15 (10) ◽

pp. 980-989 ◽

Cited By ~ 17

Author(s):

Y. Kong ◽

J. Wu ◽

D. Zhang ◽

C. Wan ◽

L. Yuan

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Disease Model ◽

Notch Signaling Pathway

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Regulation of EMT by Notch Signaling Pathway in Tumor Progression

Current Cancer Drug Targets ◽

10.2174/15680096113136660101 ◽

2013 ◽

Vol 13 (9) ◽

pp. 957-962 ◽

Cited By ~ 49

Author(s):

Yumei Li ◽

Jia Ma ◽

Xiujuan Qian ◽

Qiong Wu ◽

Jun Xia ◽

...

Keyword(s):

Tumor Progression ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway

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Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200717143109 ◽

2020 ◽

Vol 20 ◽

Author(s):

Imran Khan ◽

Sadaf Mahfooz ◽

Mohd Saeed ◽

Irfan Ahmad ◽

Irfan A. Ansari

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Notch Signaling ◽

Signaling Pathway ◽

Mtt Assay ◽

Annexin V ◽

Notch Signaling Pathway ◽

Phase Cell ◽

Ros Generation ◽

Notch 1

Background: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4′,6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7’-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.

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