RNA-seq analysis provide new insights into mapk signaling of apolipoproteinciii-induced inflammation in porcine vascular endothelial cells

Current studies have identified the multifaceted protective functions of dexmedetomidine on multiple organs. For the first time, we clarify effects of dexmedetomidine on monocyte-endothelial adherence and whether its underlying mechanism is relative to connexin43 (Cx43), a key factor regulating monocyte-endothelial adherence. U937 monocytes and human umbilical vein endothelial cells (HUVECs) were used to explore monocyte-endothelial adherence. Two special siRNAs were designed to knock down Cx43 expression on HUVECs. U937-HUVEC adhesion, adhesion-related molecules, and the activation of the MAPK (p-ERK1/2, p-p38, and p-JNK1/2) signaling pathway were detected. Dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), was given as pretreatments to HUVECs. Its effects on Cx43 and U937-HUVEC adhesion were also investigated. The results show that inhibiting Cx43 on HUVECs could attenuate the contents of MCP-1, soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and the nonprocessed variants of the adhesion molecules ICAM-1 and VCAM-1 and ultimately result in U937-HUVEC adhesion decrease. Meanwhile, the activation of MAPKs was also inhibited. U0126 (inhibiting p-ERK1/2) and SB202190 (inhibiting p38) decreased the contents of MCP-1, sICAM-1, and sVCAM-1, but SP600125 (inhibiting p-JNK1/2) had none of these effects. ICAM-1 and VCAM-1 could be regulated in a similar way. Dexmedetomidine pretreatment inhibited Cx43 on HUVECs, the activation of MAPKs, and U937-HUVEC adhesion. Therefore, we conclude that dexmedetomidine attenuates U937-HUVEC adhesion via inhibiting Cx43 on HUVECs modulating the activation of MAPK signaling pathways.

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Syndecan-1 downregulates syndecan-4 expression by suppressing the ERK1/2 and p38 MAPK signaling pathways in cultured vascular endothelial cells

Biochemistry and Biophysics Reports ◽

10.1016/j.bbrep.2021.101001 ◽

2021 ◽

Vol 26 ◽

pp. 101001

Author(s):

Takato Hara ◽

Arisa Sato ◽

Chika Yamamoto ◽

Toshiyuki Kaji

Keyword(s):

Endothelial Cells ◽

Signaling Pathways ◽

P38 Mapk ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

Vascular Endothelial ◽

Mapk Signaling Pathways

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Single-cell RNA-seq reveals lineage-specific regulatory changes of fibroblasts and vascular endothelial cells in keloid

10.1101/2020.05.14.095323 ◽

2020 ◽

Author(s):

Xuanyu Liu ◽

Wen Chen ◽

Meng Yuan ◽

Zhujun Li ◽

Tian Meng ◽

...

Keyword(s):

Endothelial Cells ◽

Single Cell ◽

Transforming Growth Factor ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Rna Seq ◽

Apoptosis Resistance ◽

Cell Lineages ◽

Medical Therapies ◽

Keloid Fibroblasts

AbstractKeloid is a benign dermal fibrotic disorder with some features similar to malignant tumors such as hyper-proliferation, apoptosis resistance and invasion. keloid remains a therapeutic challenge in terms of high recurrence rate and lack of satisfactory medical therapies, which is partially due to the incomplete understanding of keloid pathogenesis. A thorough understanding of the cellular and molecular mechanism of keloid pathogenesis would facilitate the development of novel medical therapies for this disease. Here, we performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of the keloid tissue, which included 21 cell clusters assigned to 11 cell lineages. Differential proportion analysis revealed significant expansion for fibroblasts and vascular endothelial cells in keloid compared with control, reflecting their strong association with keloid pathogenesis. We then identified five previously unrecognized subpopulations of keloid fibroblasts and four subpopulations of vascular endothelial cells. Comparative analyses were performed to identify the dysregulated pathways, regulators and ligand-receptor interactions for keloid fibroblasts and vascular endothelial cells, the two important cell lineages in keloid pathogenesis and for medical interventions. Our results highlight the roles of transforming growth factor beta and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloid. Critical regulators and signaling receptors implicated in the fibrogenesis of other fibrotic disorders, such as TWIST1, FOXO3, SMAD3 and EPHB2, ranked at the top in the regulatory network of keloid fibroblasts. In addition, tumor-related pathways such as negative regulation of PTEN transcription were found to be activated in keloid fibroblasts and vascular endothelial cells, which may be responsible for the malignant features of keloid. Our study put novel insights into the pathogenesis of keloid, and provided potential targets for medical therapies. Our dataset also constitutes a valuable resource for further investigations of the mechanism of keloid pathogenesis.

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107 FVIIa Prevents the Progressive Hemorrhaging of a Brain Contusion by Protecting Microvessels Via Formation of the TF-FVIIa-FXa Complex

Neurosurgery ◽

10.1093/neuros/nyx417.107 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 221-222

Author(s):

Qiang Yuan

Keyword(s):

Endothelial Cells ◽

Signaling Pathways ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

Coagulation Cascade ◽

Cell Protein ◽

Vascular Endothelial ◽

Brain Contusion ◽

Microvessel Endothelial Cells

Abstract INTRODUCTION Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant human activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. METHODS Controlled cortical impact model of mouse brain contusion was used to examine whether decreased FVII activity would directly lead to the occurrence of progressive hemorrhaging in mice and whether administration of FVIIa would prevent the delayed catastrophic structural failure of microvessels and the progressive hemorrhaging of brain contusions by protecting vascular endothelial cells via formation of the ternary TF FVIIa FXa complex. Activations of p44/42 MAPK, p38 MAPK, and p65 NF-kB signaling pathways by ternary TF FVIIa FXa complex were tested by WB in HUVECs. RESULTS >The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions. Administration of FVII prevented the progression of hemorrhaging from cerebral contusions by protecting microvessel endothelial cells in the penumbra of the contusion. The present study also showed that the ternary TF FVIIa FXa complex cleaved endogenous protease-activated receptor 2 (PAR2) on endothelial cells, activated the p44/42 mitogen-activated protein kinase (MAPK) signaling cascade, and inhibited p65 nuclear factor-kB (NF-kB) signaling. Furthermore, exposure to ternary TF FVIIa FXa protected endothelial cells from thrombin- or inflammatory cytokine-induced apoptosis. Although activation of the p44/42 MAPK signaling pathway is endothelial cell protein C receptor (EPCR)-dependent, inhibition of the p65 NF-kB signaling pathway is EPCR independent; thus, the regulation mechanism underlying the effects of TF FVIIa FXa in vascular endothelial cells appears to be multiple signaling pathways. CONCLUSION In summary, the present findings demonstrated that FVIIa prevented the progressive hemorrhaging of brain contusions by protecting microvessel endothelial cells via the formation of the ternary TF FVIIa FXa complex. These findings are novel and of great clinical significance because FVIIa is used to prevent the progressive hemorrhaging of brain contusions in humans.

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Shear Stress Activates p60src-Ras-MAPK Signaling Pathways in Vascular Endothelial Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.18.2.227 ◽

1998 ◽

Vol 18 (2) ◽

pp. 227-234 ◽

Cited By ~ 166

Author(s):

Shila Jalali ◽

Yi-Shuan Li ◽

Mohammad Sotoudeh ◽

Suli Yuan ◽

Song Li ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Signaling Pathways ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

Vascular Endothelial ◽

Mapk Signaling Pathways

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Functional consequences of complement activation on vascular endothelial cells – Results of a pilot RNA seq study

Molecular Immunology ◽

10.1016/j.molimm.2018.06.191 ◽

2018 ◽

Vol 102 ◽

pp. 204

Author(s):

Magdalena Riedl ◽

Erin Jacobs ◽

Alan Zhou ◽

Daniel Schlam ◽

Sergio Grinstein ◽

...

Keyword(s):

Endothelial Cells ◽

Complement Activation ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Rna Seq ◽

Functional Consequences

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Baicalin modulates apoptosis via RAGE, MAPK, and AP-1 in vascular endothelial cells duringHaemophilus parasuisinvasion

Innate Immunity ◽

10.1177/1753425919856078 ◽

2019 ◽

Vol 25 (7) ◽

pp. 420-432 ◽

Cited By ~ 2

Author(s):

Shulin Fu ◽

Wenhua Zhao ◽

Chunhong Xiong ◽

Ling Guo ◽

Jing Guo ◽

...

Keyword(s):

Endothelial Cells ◽

Protein Kinase ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

S Phase ◽

Vascular Endothelial ◽

Phase Arrest ◽

S Phase Arrest ◽

Apoptotic Genes

Glässer’s disease, caused by Haemophilus parasuis, is a chronic disease related to an inflammatory immune response. Baicalin exerts important biological functions. In this study, we explored the protective efficacy of treatment with baicalin and the potential mechanism of activation of the MAPK signaling pathway in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis. H. parasuis stimulated expression of receptor for advanced glycation end products, induced a significant increase in the level of protein kinase-α and protein kinase-δ phosphorylation, and significantly up-regulated ERK, c-Jun N-terminal kinase, and p38 phosphorylation in PAVECs. H. parasuis also up-regulated the levels of apoptotic genes ( Bax, C-myc, and Fasl) and the expression levels of c-Jun and c-Fos, and induced S-phase arrest in PAVECs. However, treatment with baicalin inhibited expression of RAGE, suppressed H. parasuis-induced protein kinase-α and protein kinase-δ phosphorylation, reduced ERK, c-Jun N-terminal kinase, and p38 phosphorylation, down-regulated apoptotic genes ( Bax, C-myc, and Fasl), attenuated phospho-c-Jun production from the extracellular to the nuclei, and reversed S-phase arrest in PAVECs. In conclusion, baicalin treatment inhibited the MAPK signaling pathway, thereby achieving its anti-inflammatory responses, which provides a new strategy to control H. parasuis infection.

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MicroRNA-126 attenuates CXCL-8 induced effects on proliferation, migration, apoptosis and MAPK signaling activity of vascular endothelial cells cultured in high glucose

Bulletin of Experimental Biology and Medicine ◽

10.47056/0365-9615-2021-171-2-164-169 ◽

2021 ◽

Vol 171 (2) ◽

pp. 164-169

Author(s):

S.Q. Zhang ◽

◽

L.L. Wang ◽

Y.T. Li ◽

G. Wang ◽

...

Keyword(s):

Endothelial Cells ◽

High Glucose ◽

Vascular Endothelial Cells ◽

Mapk Signaling ◽

Vascular Endothelial ◽

Signaling Activity ◽

Cells Cultured

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Human Peripheral Blood-Derived Endothelial Colony-Forming Cells Are Highly Similar to Mature Vascular Endothelial Cells yet Demonstrate a Transitional Transcriptomic Signature

Cells ◽

10.3390/cells9040876 ◽

2020 ◽

Vol 9 (4) ◽

pp. 876 ◽

Cited By ~ 3

Author(s):

Anton G. Kutikhin ◽

Alexey E. Tupikin ◽

Vera G. Matveeva ◽

Daria K. Shishkova ◽

Larisa V. Antonova ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Gene Expression Profile ◽

Vascular Endothelial Cells ◽

Vascular Grafts ◽

Global Gene Expression ◽

Tube Formation ◽

Vascular Endothelial ◽

Rna Seq ◽

Endothelial Colony Forming Cells

Endothelial colony-forming cells (ECFC) are currently considered as a promising cell population for the pre-endothelialization or pre-vascularization of tissue-engineered constructs, including small-diameter biodegradable vascular grafts. However, the extent of heterogeneity between ECFC and mature vascular endothelial cells (EC) is unclear. Here, we performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC), and human umbilical vein endothelial cells (HUVEC). Characterization of the abovementioned cell populations was carried out by immunophenotyping, tube formation assay, and evaluation of proliferation capability while global gene expression profiling was conducted by means of RNA-seq. ECFC were similar to HUVEC in terms of immunophenotype (CD31+vWF+KDR+CD146+CD34-CD133-CD45-CD90-) and tube formation activity yet had expectedly higher proliferative potential. HCAEC and HUVEC were generally similar to ECFC with regards to their global gene expression profile; nevertheless, ECFC overexpressed specific markers of all endothelial lineages (NRP2, NOTCH4, LYVE1), in particular lymphatic EC (LYVE1), and had upregulated extracellular matrix and basement membrane genes (COL1A1, COL1A2, COL4A1, COL4A2). Proteomic profiling for endothelial lineage markers and angiogenic molecules generally confirmed RNA-seq results, indicating ECFC as an intermediate population between HCAEC and HUVEC. Therefore, gene expression profile and behavior of ECFC suggest their potential to be applied for a pre-endothelialization of bioartificial vascular grafts, whereas in terms of endothelial hierarchy they differ from HCAEC and HUVEC, having a transitional phenotype.

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