MiR-548j-5p regulates angiogenesis in peripheral artery disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee CY
PROVIDER: S-EPMC8764034 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Peripheral artery disease (PAD) poses a great challenge to society, with a growing prevalence in the upcoming years. Patients in the severe stages of PAD are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden. Furthermore, PAD is one of the major complications of diabetic patients, who have higher risk to develop critical limb ischemia, the most severe manifestation of PAD, and thus have a poor prognosis. Hence, there is an urgent need to develop an effective therapeutic strategy to treat this disease. Therapeutic angiogenesis has raised concerns for more than two decades as a potential strategy for treating PAD, especially in patients without option for surgery-based therapies. Since the discovery of gene-based therapy for therapeutic angiogenesis, several approaches have been developed, including cell-, protein-, and small molecule drug-based therapeutic strategies, some of which have progressed into the clinical trial phase. Despite its promising potential, efforts are still needed to improve the efficacy of this strategy, reduce its cost, and promote its worldwide application. In this review, we highlight the current progress of therapeutic angiogenesis and the issues that need to be overcome prior to its clinical application.
| S-EPMC9274744 | biostudies-literature
Project description:BackgroundAngiogenesis plays an important role in peripheral artery disease (PAD) and angiogenesis-related proteins may act as prognostic biomarkers. This study assesses the potential for angiogenesis-related proteins to predict adverse events associated with PAD.MethodsThis was a case-control study. Patients with PAD (n = 250) and without PAD (n = 125) provided blood samples and were followed prospectively for three years. Concentrations of 17 angiogenesis-related proteins were measured in plasma. The incidence of major adverse limb event (MALE), defined as a composite of major amputation or vascular intervention, was the primary outcome. Worsening PAD status, defined as a drop in ankle brachial index ≥ 0.15, was the secondary outcome. Multivariable regression adjusted for baseline characteristics was conducted to determine the prognostication value of angiogenesis-related proteins in predicting MALE.FindingsRelative to patients without PAD, 8 proteins related to angiogenesis were expressed differentially in PAD patients. Worsening PAD status and MALE were observed in 52 (14%) and 83 (22%) patients, respectively. Hepatocyte growth factor (HGF) was the most reliable predictor of MALE (adjusted HR 0.79, 95% CI 0.15-0.86). Compared to individuals with high HGF, patients with low HGF had a decreased three-year freedom from MALE [66% vs 88%, p = 0.001], major amputation [93% vs 98%, p = 0.023], vascular intervention [68% vs 88%, p = 0.001], and worsening PAD status [81% vs 91%, p = 0.006].InterpretationMeasuring plasma levels of HGF in individuals with PAD can assist in identifying patients at elevated risk of adverse events related to PAD who may benefit from additional evaluation or treatment.
| S-EPMC10559913 | biostudies-literature
Project description:BackgroundAngiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis.MethodsThe expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot. Transient cell transfection was performed using the Lipofectamine 3000 reagent. The RNA-binding protein immunoprecipitation (RNA-IP) and the RNA pull-down assays were used to detect the interaction between FUS and circ_002136. The dual-luciferase reporter assay system was performed to detect the binding sites of circ_002136 and miR-138-5p, miR-138-5p and SOX13. The chromatin immunoprecipitation (ChIP) assays were used to examine the interactions between transcription factor SOX13 and its target proteins .ResultsWe demonstrated that down-regulation of FUS or circ_002136 dramatically inhibited the viability, migration and tube formation of U87 glioma-exposed endothelial cells (GECs). MiR-138-5p was down-regulated in GECs and circ_002136 functionally targeted miR-138-5p in an RNA-induced silencing complex (RISC). Inhibition of circ_002136, combined with the restoration of miR-138-5p, robustly reduced the angiogenesis of GECs. As a target gene of miR-138-5p, SOX13 was overexpressed in GECs and was proved to be involved in circ_002136 and miR-138-5p-mediated angiogenesis in gliomas. In addition, we found that SOX13 was directly associated with and activated the SPON2 promoter, thereby up-regulating the expression of SPON2 at the transcriptional level. Knockdown of SPON2 suppressed the angiogenesis in GECs. More important, SOX13 activated the FUS promoter and increased its expression, forming a feedback loop.ConclusionOur data suggests that the feedback loop of FUS/circ_002136/miR-138-5p/SOX13 played a crucial role in the regulation of angiogenesis in glioma. This also provides a potential target and an alternative strategy for combined glioma therapy.
| S-EPMC6368736 | biostudies-literature
Project description:MiRNAs have been shown to alter both protein expression and secretion in different cellular contexts. By combining in vitro, in vivo and in silico techniques, we demonstrated that overexpression of pre-miR-1307 reduced the ability of breast cancer cells to induce endothelial cell sprouting and angiogenesis. However, the molecular mechanism behind this and the effect of the individual mature miRNAs derived from pre-miR-1307 on protein secretion and is largely unknown. Here, we overexpressed miR-1307-3p|0, -3p|1 and 5p|0 in MDA-MB-231 breast cancer cells and assessed the impact of miRNA overexpression on protein secretion by Mass Spectrometry. Unsupervised hierarchical clustering revealed a distinct phenotype induced by overexpression of miR-1307-5p|0 compared to the controls and to the 5’isomiRs derived from the 3p-arm. Together, our results suggest different impacts of miR-1307-3p and miR-1307-5p on protein secretion which is in line with our in vitro observation that miR-1307-5p, but not the isomiRs derived from the 3p-arm reduce endothelial cell sprouting in vitro. Hence these data support the hypothesis that miR-1307-5p is at least partly responsible for impaired vasculature in tumors overexpressing pre-miR-1307.
2024-12-11 | PXD041087 | Pride
Project description:Therapeutic angiogenesis utilizing genetic and cellular modalities in the treatment of arterial obstructive diseases continues to evolve. This is, in part, because the mechanism of vasculogenesis, angiogenesis, and arteriogenesis (the three processes by which the body responds to obstruction of large conduit arteries) is a complex process that is still under investigation. To date, the majority of human trials utilizing molecular, genetic, and cellular modalities for therapeutic angiogenesis in the treatment of peripheral artery disease (PAD) have not shown efficacy. Consequently, the current available knowledge is yet to be translated into novel therapeutic approaches for the treatment of PAD. The aim of this review is to discuss relevant scientific and clinical advances in therapeutic angiogenesis and their potential application in the treatment of ischemic diseases of the peripheral arteries. Additionally, this review article discusses past and recent developments, such as some unconventional approaches that have the potential to be applied as therapeutic targets. The article also includes advances in the delivery of genetic, cellular, and bioactive endothelial growth factors.
| S-EPMC3760002 | biostudies-literature
Project description:Peripheral arterial disease (PAD) is a major health care problem. There have been limited advances in medical therapies, and a huge burden of symptomatic patients with intermittent claudication and critical limb ischemia who have limited treatment options. Angiogenesis is the growth and proliferation of blood vessels from existing vasculature. For approximately 2 decades, "therapeutic angiogenesis" has been studied as an investigational approach to treat patients with symptomatic PAD. Despite literally hundreds of positive preclinical studies, results from human clinical studies thus far have been disappointing. Here we present an overview of where the field of therapeutic angiogenesis stands today and examine lessons learned from previously conducted clinical trials. The objective is not to second-guess past efforts but to place the lessons in perspective to allow for trial success in the future to improve agent development, trial design, and ultimately, clinical outcomes for new therapeutics for PAD.
| S-EPMC5802410 | biostudies-literature
Project description:BackgroundVascular dementia (VaD) mainly results from cerebral vascular lesions and tissue changes, which contribute to neurodegenerative processes. Effective therapeutic approaches to targeting angiogenesis may reduce mortality of VaD. Endothelial progenitor cells (EPCs) play a key role in postnatal angiogenesis. Many exosomal microRNAs (exo-miRNAs) have been reported to involve in the development of dementia. The present study was designed to investigate whether the expression profile of the exo-miRNAs is significantly altered in patients with VaD and to reveal the function of differentially expressed miRNAs and the relevant mechanisms in EPC-mediated angiogenesis in VaD rat model.ResultsExosomes isolated from serum of patients with VaD (n = 7) and age-matched control subjects (n = 7), and miRNA sequencing and bioinformatics analysis found that circulating exosome miRNA-155-5p, miRNA-154-5p, miR-132-5p, and miR-1294 were upregulated in patients with VaD. The expression of miRNA-154-5p was further verified to be upregulated in clinical samples (n = 23) and 2-vessel occlusion-induced VaD rat model by reverse transcription quantitative PCR (RT-qPCR). Notably, miRNA-154-5p inhibition in bone marrow-EPCs (BM-EPCs) from VaD rats improved EPC functions, including tube formation, migration, and adhesion, and elevated concentrations of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α). The mRNA levels of ICAM-1, VCAM-1, and MCP-1 were reduced in miRNA-154-5p-inhibited EPCs. In addition, miRNA-154-5p inhibition increased the level of superoxide dismutase (SOD), and decreased reactive oxygen species (ROS) in EPCs. PRKAA2 was chosen as a promising target gene of miR-154-5p, and miRNA-154-5p inhibition upregulated the protein expression of AMPKα2. Furthermore, upregulation of miR-154-5p markedly diminished EPC functions and inhibited angiogenesis following EPC transplantation in VaD rats.ConclusionCirculating exo-miR-154-5p was upregulated in patients with VaD, and miR-154-5p upregulation was associated with impaired EPC functions and angiogenesis in VaD rat model. Therefore, miR-154-5p is a promising biomarker and therapeutic strategy for VaD.
| S-EPMC9372489 | biostudies-literature
Project description:BackgroundDue to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1.MethodsTMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue (TB), immunohistochemical (IHC) staining, Western blotting (WB) and RT-qPCR. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. WB, RT-qPCR, IHC and TB were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo chorioallantoic membrane (CAM) assay and WB.ResultsIn the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged, and miR-21-5p and UAC model were shown to affect the expression of Spry1, IL-1β, MMP-13, and VEGF. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1β, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway.ConclusionThis study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.
| S-EPMC7195789 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) have been reported to be associated with the progression of coronary artery disease (CAD). In our previous study, the levels of lncRNA uc003pxg.1 were upregulated in patients with CAD compared with those in control subjects. However, the role and underlying mechanism of the effects of uc003pxg.1 in CAD remain unknown. Therefore, the aim of the present study was to investigate the expression pattern and biological function of uc003pxg.1 in CAD. First, uc003pxg.1 expression levels were assessed in peripheral blood mononuclear cells isolated from patients with CAD by reverse transcription‑quantitative (RT‑q)PCR. The results demonstrated that the levels of uc003pxg.1 were significantly upregulated (~4.6‑fold) in samples from 80 patients with CAD compared with those in 80 healthy subjects. Subsequently, the present study demonstrated that small interfering RNA‑mediated uc003pxg.1 knockdown inhibited human umbilical vein endothelial cell (HUVEC) proliferation and migration, which was analyzed using the Cell Counting Kit‑8, cell cycle, EdU and Transwell assays. Additionally, the results of RT‑qPCR and western blot analyses revealed that uc003pxg.1 regulated the mRNA and protein levels of cyclin D1 and cyclin‑dependent kinase. Through high‑throughput sequencing and dual‑luciferase reporter assays, the present study demonstrated that microRNA (miR)‑25‑5p was a downstream target of uc003pxg.1. Further experiments verified that uc003pxg.1 regulated HUVEC proliferation and migration via miR‑25‑5p. The results of the present study may enhance the current understanding of the role of lncRNA uc003pxg.1 in CAD.
| S-EPMC8262661 | biostudies-literature
Project description:Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of i) osteoblasts and chondrocytes genes expression, ii) joint inflammation cytokines releases and iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.
| S-EPMC7957523 | biostudies-literature