Downregulation of acylglycerol kinase suppresses high glucose-induced endothelial-mesenchymal transition in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway

2021 ◽  
Author(s):  
Haijing Wang ◽  
Zhuolei Feng ◽  
Xue Han ◽  
Yue Xing ◽  
Xiaomei Zhang
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
High Glucose ◽  
Notch Signaling Pathway ◽  
Mesenchymal Transition ◽  
Intrinsic Factors ◽  
Acylglycerol Kinase ◽  
Notch Pathways ◽  
Endothelial Mesenchymal Transition

The endothelial-mesenchymal transition (EndMT) participates in the progression of diabetic retinopathy (DR), but cell-intrinsic factors modulating this process remain elusive. In this study, we explored the role of lysophosphatidic acid (LPA)-producing enzyme, acylglycerol kinase (AGK) in the EndMT of human retinal microvascular endothelial cells (HRECs) under high glucose (HG) conditions. We found that AGK was significantly elevated in HG-treated cells. In addition, AGK knockdown reversed the HG-induced EndMT in HRECs, which was evidenced by the increased epithelial markers (CD31 and VE-cadherin) and decreased mesenchymal markers (FSP1 and α-SMA). Furthermore, downregulation of AGK inhibited the HG-induced activation of TGF-β/Notch pathways, whereas exogenous TGF-β1 (10 ng/ml) impeded the inhibitory effects of AGK knockdown on HG-induced EndMT in HRECs. Additionally, the silence of AGK abolished the HG-induced upregulation of LPA and its receptor LPAR1, and overexpression of LPAR1 further rescued the AGK knockdown-mediated inhibition of the EndMT process. In conclusion, we demonstrate that downregulation of acylglycerol kinase suppresses high glucose-induced endothelial-mesenchymal transition in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway, indicating that AGK might be a potential therapeutic target for the treatment of DR.

scholarly journals Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1264-1273 ◽  
Author(s):  
Melanie G. Cornejo ◽  
Vinciane Mabialah ◽  
Stephen M. Sykes ◽  
Tulasi Khandan ◽  
Cristina Lo Celso ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Hematopoietic Stem Cell ◽  
Stem Cell Differentiation ◽  
Notch Signaling Pathway ◽  
Developmental Pathways ◽  
Lineage Specification ◽  
Hematopoietic Stem

Abstract The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.

scholarly journals MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Bin Yang ◽  
Chunping Wang ◽  
Hui Xie ◽  
Yiwu Wang ◽  
Jiagan Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Notch Signaling Pathway ◽  
Advanced Hepatocellular Carcinoma ◽  
Targeted Agents ◽  
Mesenchymal Transition ◽  
Molecular Targeted Agents ◽  
Hcc Cells

Abstract Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

scholarly journals Epidermoid cyst in a patient with Alagille syndrome: Coincidence or connection?

2020 ◽  
Vol 11 ◽  
pp. 432
Author(s):  
Akhil Surapaneni ◽  
John Kuo ◽  
Min Wang ◽  
Ramsey Ashour
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Epidermoid Cyst ◽  
Alagille Syndrome ◽  
Notch Signaling Pathway ◽  
Syndrome Patient ◽  
Benign Lesions ◽  
Genetic Syndrome ◽  
Epidermoid Cysts

Background: Alagille syndrome is a rare genetic syndrome, which arises due to defects in the Notch signaling pathway, resulting in liver, cardiopulmonary, renal, skeletal, and ophthalmologic problems, among others. Epidermoid cysts are rare congenital benign lesions that develop from ectopic ectodermal cell rests formed during neurulation. Case Description: A 24-year-old Alagille syndrome patient presented with hearing loss and was found to have a sizable posterior fossa mass. He underwent craniotomy for uneventful resection of the lesion, which was found to be an epidermoid cyst. Conclusion: While our case may represent a coincidental occurrence of two pathologies presenting together, given that epidermoid cysts arise from aberrant neurulation, and in light of the crucial role of the Notch signaling pathway both in normal neurogenesis and in the pathogenesis of Alagille syndrome, we hypothesize a possible association between these entities.

scholarly journals The Carcinogenic Role of the Notch Signaling Pathway in the Development of Hepatocellular Carcinoma

2019 ◽  
Vol 10 (6) ◽  
pp. 1570-1579 ◽  
Author(s):  
Qinfeng Huang ◽  
Junhong Li ◽  
Jinghui Zheng ◽  
Ailing Wei
Keyword(s):  
Hepatocellular Carcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

scholarly journals SATB1 promotes epithelial-mesenchymal transition via Notch signaling pathway in colorectal cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921985889
Author(s):  
Jun Tang ◽  
Jingfang Yang
Keyword(s):  
Colorectal Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Biomarker ◽  
Notch Signaling Pathway ◽  
Vital Role ◽  
Cell Models ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Target

Epithelial-mesenchymal transition (EMT) is essential for initiation of colorectal cancer (CRC) metastasis, but the diver proteins of EMT remain unclear. Special AT-rich sequence-binding protein 1 (SATB1) was found to be overexpressed in CRC cell lines, and its expression level was positively correlated with CRC progression. Strikingly, EMT process was regulated by SATB1, as SATB1 overexpression upregulated E-cadherin and SATB1 knockdown inhibited N-cadherin cell models. Mechanistically, SATB1 promoted EMT-mediated CRC metastasis via activation of Notch signaling pathway. Taken together, SATB1 plays a vital role in CRC metastasis and may act as a novel prognostic biomarker and a promising therapeutic target for CRC.

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