KAP1 silencing relieves OxLDL-induced vascular endothelial dysfunction by down-regulating LOX-1

Yan, Tianqing; Liang, Chang; Fan, Haidi; Zhou, Wei; Huang, Linyan; Qi, Suhua; Wang, Wan; Ma, Ping

doi:10.1042/bsr20200821

Cited by 5 publications

(4 citation statements)

References 37 publications

(50 reference statements)

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“…KAP1 enhances cell proliferation in glioblastoma by promoting autophagy [29]. In addition, knockdown of KAP1 abolished the effect of OxLDL on vascular endothelial dysfunction [30]. The positive expression of KAP1 is relative to phenotypic switching of human aortic smooth muscle cells (HASMCs) stimulated by platelet-derived growth factor subunit B homodimer (PDGF-BB).…”

Section: Introductionmentioning

confidence: 99%

KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells

et al. 2023

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Background Osteoblast phenotypic transition in vascular smooth muscle cells (VSMCs) has been unveiled as a common cause of vascular calci cation (VC). Krüppel-Associated Box (KRAB)-Associated Protein 1(KAP1) is a transcriptional corepressor that modulates various intracellular pathological processes from gene expression to DNA repair to signal transduction. However, the function and mechanism of KAP1 on the osteoblastic differentiation of VSMCs have not been evaluated yet. Methods and resultsWe demonstrate that the expression of KAP1 in VSMCs is signi cantly enhanced in vivo and in vitro calci cation models. Downregulating the expression of KAP1 suppresses the osteoblast phenotypic transition of VSMCs, which is indicated by a decrease in the expression of osteoblast marker collagenase type I (COL I) and an increase in the expression of VSMC marker α-smooth muscle actin (α-SMA). Conversely, exogenous overexpression of KAP1 could promote osteoblast phenotypic transition of VSMCs. Moreover, KAP1 upregulated the expression of RUNX family transcription factor 2 (Runx2), an inducer of osteoblast that positively regulates many osteoblast-related genes, such as COL I. Evaluation of the potential mechanism demonstrated that KAP1 promoted osteoblast phenotypic transition of VSMCs by activating the extracellular regulated protein kinases (ERK) signaling pathway, which could activate Runx2. In support of this nding, KAP1-induced cell osteoblast phenotypic transition is abolished by treatment with PD0325901, a speci c ERK inhibitor.Conclusions The present study suggested that KAP1 participated in the osteoblast differentiation of VSMCs via the ERK/Runx2 cascade and served as a potential diagnostics and therapeutics target for vascular calci cation.

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Section: Introductionmentioning

confidence: 99%

KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells

et al. 2023

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“…The procedures of real-time PCR were the same as in our previous work [28]. Primer sequences employed in this study are listed: PCNA primers: sense, TTT CAC AAA AGC CAC TCC ACTG; antisense, CTT TAA GTG TCC CAT GTC AGC AAT .…”

Section: Quantitative Real-time Fluorescent Polymerase Chain Reaction...mentioning

confidence: 99%

KAP1 phosphorylation promotes the survival of neural stem cells after ischemia/reperfusion by maintaining the stability of PCNA

et al. 2022

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Aims To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after cerebral ischemic/reperfusion (I/R). Methods The apoptosis and proliferation of C17.2 cells transfected with the p-KAP1-expression plasmids and the expression of proliferation cell nuclear antigen (PCNA) and p-KAP1 were detected by immunofluorescence and Western blotting after the Oxygen Glucose deprivation/reperfusion model (OGD/R). The interaction of p-KAP1 and CUL4A with PCNA was analyzed by immunoprecipitation. In the rats MCAO model, we performed the adeno-associated virus (AAV) 2/9 gene delivery of p-KAP1 mutants to verify the proliferation of endogenous NSCs and the colocalization of PCNA and CUL4A by immunofluorescence. Results The level of p-KAP1 was significantly down-regulated in the stroke model in vivo and in vitro. Simulated p-KAP1(S824) significantly increased the proliferation of C17.2 cells and the expression of PCNA after OGD/R. Simulated p-KAP1(S824) enhanced the binding of p-KAP1 and PCNA and decreased the interaction between PCNA and CUL4A in C17.2 cells subjected to OGD/R. The AAV2/9-mediated p-KAP1(S824) increased endogenous NSCs proliferation, PCNA expression, p-KAP1 binding to PCNA, and improved neurological function in the rat MCAO model. Conclusions Our findings confirmed that simulated p-KAP1(S824) improved the survival and proliferation of endogenous NSCs. The underlying mechanism is that highly expressed p-KAP1(S824) promotes binding to PCNA, and inhibits the binding of CUL4A to PCNA. This reduced CUL4A-mediated ubiquitination degradation to increase the stability of PCNA and promote the survival and proliferation of NSCs.

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“…Endothelial cell lines, in particular derived from the human umbilical cord (HUVEC), serve mostly for this task to evaluate the effects of biochemical and/or mechanical damage, intended as first triggers for the development of the atherosclerotic lesion. These models of endothelial damage are useful to dissect the pathways that result in being dysregulated after contact with oxidative LDL ( 178 , 179 ), with free fatty acids ( 180 , 181 ), and in conditions of reduced shear stress or mechanical insult ( 182 – 184 ). Positive effects of atherosclerosis sign attenuation were disclosed by several in vitro studies using microRNAs on activated endothelial cells: miR-106a-5p, miR-144-5p, miR-200a, miR-490, and miR-500 ( 185 – 189 ).…”

Section: Acquired Heart Diseasesmentioning

confidence: 99%

Toward the Effective Bioengineering of a Pathological Tissue for Cardiovascular Disease Modeling: Old Strategies and New Frontiers for Prevention, Diagnosis, and Therapy

Iop

2021

Front. Cardiovasc. Med.

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Cardiovascular diseases (CVDs) still represent the primary cause of mortality worldwide. Preclinical modeling by recapitulating human pathophysiology is fundamental to advance the comprehension of these diseases and propose effective strategies for their prevention, diagnosis, and treatment. In silico, in vivo, and in vitro models have been applied to dissect many cardiovascular pathologies. Computational and bioinformatic simulations allow developing algorithmic disease models considering all known variables and severity degrees of disease. In vivo studies based on small or large animals have a long tradition and largely contribute to the current treatment and management of CVDs. In vitro investigation with two-dimensional cell culture demonstrates its suitability to analyze the behavior of single, diseased cellular types. The introduction of induced pluripotent stem cell technology and the application of bioengineering principles raised the bar toward in vitro three-dimensional modeling by enabling the development of pathological tissue equivalents. This review article intends to describe the advantages and disadvantages of past and present modeling approaches applied to provide insights on some of the most relevant congenital and acquired CVDs, such as rhythm disturbances, bicuspid aortic valve, cardiac infections and autoimmunity, cardiovascular fibrosis, atherosclerosis, and calcific aortic valve stenosis.

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KAP1 silencing relieves OxLDL-induced vascular endothelial dysfunction by down-regulating LOX-1

Cited by 5 publications

References 37 publications

KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells

KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells

KAP1 phosphorylation promotes the survival of neural stem cells after ischemia/reperfusion by maintaining the stability of PCNA

Toward the Effective Bioengineering of a Pathological Tissue for Cardiovascular Disease Modeling: Old Strategies and New Frontiers for Prevention, Diagnosis, and Therapy

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