Abstract:
:Background: Lysophosphatidic acid (LPA) is a small glycerophospholipid that acts as a potent extracellular signal in various biological processes and diseases. Our previous work demonstrated that the expression of the LPA receptors LPA1 and LPA3 is elevated in the early postnatal heart. However, the role of this stage-specific expression of LPA1 and LPA3 in the heart is unknown. Methods and Results: By using LPA3 and LPA1 knockout mice, and neonatal SD rats treated with Ki16425 (LPA1/LPA3 inhibitor), we found that the number of proliferating cardiomyocytes, detected by coimmunostaining pH3, Ki67 or BrdU with cardiac troponin T, was significantly decreased in the LPA3 knockout mice and the Ki16425-treated rats but not in the LPA1 knockout mice during the first week of postnatal life. Using a myocardial infarction (MI) model, we found that cardiac function and the number of proliferating cardiomyocytes were decreased in the neonatal LPA3 KO mice and increased in the AAV9-mediated cardiac-specific LPA3 overexpression mice. By using lineage tracing and AAV9-LPA3, we further found that LPA3 overexpression in adult mice enhances cardiac function and heart regeneration as assessed by pH3-, Ki67-, and Aurora B-positive cardiomyocytes and clonal cardiomyocytes after MI. Genome-wide transcriptional profiling and additional mechanistic studies showed that LPA induces cardiomyocyte proliferation through the PI3K/AKT, BMP-Smad1/5, Hippo/YAP and MAPK/ERK pathways in vitro, whereas only ERK was confirmed to be activated by LPA-LPA3 signaling in vivo. Conclusion: Our study reports that LPA3-mediated LPA signaling is a crucial factor for cardiomyocyte proliferation in the early postnatal heart. Cardiac-specific LPA3 overexpression improved cardiac function and promoted cardiac regeneration after myocardial injury induced by MI. This finding suggested that activation of LPA3 potentially through AAV-mediated gene therapy might be a therapeutic strategy to improve the outcome after MI.
journal_name
Theranosticsjournal_title
Theranosticsauthors
Wang F,Liu S,Pei J,Cai L,Liu N,Liang T,Dong X,Cong X,Chun J,Chen J,Hu S,Chen Xdoi
10.7150/thno.47913subject
Has Abstractpub_date
2020-08-29 00:00:00pages
10892-10907issue
24issn
1838-7640pii
thnov10p10892journal_volume
10pub_type
杂志文章相关文献
Theranostics文献大全abstract::RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.7866
更新日期:2014-08-13 00:00:00
abstract::Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imag...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.45825
更新日期:2020-08-15 00:00:00
abstract::Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance signifi...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.3582
更新日期:2012-01-01 00:00:00
abstract::Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies. However, despite significant advances in recent years, this field still suffers from poor data reproducibility. This is especially true in cases of infants, conside...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.31502
更新日期:2019-06-19 00:00:00
abstract::Rationale: The evaluation of early treatment response is critical for patient prognosis and treatment planning. When the current methods rely on invasive protocols that evaluate the expression of DNA damage markers on patient biopsy samples, we aim to evaluate a non-invasive PET imaging approach to monitor the early e...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44772
更新日期:2020-04-27 00:00:00
abstract::Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could a...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.17073
更新日期:2017-01-05 00:00:00
abstract::The relatively new field of nanotheranostics combines the advantages of in vivo diagnosis with the ability to administer treatment through a single nano-sized carrier, offering new opportunities for cancer diagnosis and therapy. Nanotheranostics has facilitated the development of nanomedicine through direct visualizat...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.4381
更新日期:2012-01-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a chronic and diffuse form of interstitial lung disease of unknown etiology with a fatal outcome. Although various strategies for IPF have been developed over the last few decades, no significant positive impact on the prognosis of IPF has been observed. According to the current ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.48152
更新日期:2021-01-01 00:00:00
abstract::Aim: Immune responsive 12/15 lipoxygenase (12/15LOX)-orchestrate biosynthesis of essential inflammation-resolution mediators during acute inflammatory response in post-myocardial infarction (MI). Lack of 12/15LOX dampens proinflammatory mediator 12-(S)-hydroxyeicosatetraenoic acid (12-(S)-HETE), improves post-MI survi...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.51183
更新日期:2021-01-01 00:00:00
abstract::Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy....
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.41382
更新日期:2020-03-04 00:00:00
abstract::Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.16425
更新日期:2016-09-25 00:00:00
abstract::Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.17573
更新日期:2017-04-10 00:00:00
abstract::A major challenge in photodynamic therapy (PDT) is the development of new tumor-targeting photosensitizers. The tumor-specific activation is considered to be an effective strategy for designing these photosensitizers. Herein, we describe a novel tumor-pH-responsive supramolecular photosensitizer, LDH-ZnPcS8, which is ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.18861
更新日期:2017-07-07 00:00:00
abstract::Recently, researchers identified a distinct vessel subtype called type H vessels that couple angiogenesis and osteogenesis. We previously found that type H vessels are reduced in ovariectomy (OVX)-induced osteoporotic mice, and preosteoclasts are able to secrete platelet-derived growth factor-BB (PDGF-BB) to stimulate...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.22144
更新日期:2018-03-28 00:00:00
abstract::Purpose: Clinical success of precision medicine is severely limited by de novo or acquired drug resistance. It remains a clinically unmet need to treat these patients. Tumor suppressor genes (TSGs) play a critical role in tumorigenesis and impact the therapeutic effect of various treatments. Experimental Design: Using...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44829
更新日期:2020-09-16 00:00:00
abstract::Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.27794
更新日期:2019-01-21 00:00:00
abstract::Background: Metastasis is the major reason for high recurrence rates and poor survival among patients with colorectal cancer (CRC). However, the underlying molecular mechanism of CRC metastasis is unclear. This study aimed to investigate the role of forkhead box K2 (FOXK2), one of the most markedly increased FOX genes...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.31716
更新日期:2019-05-31 00:00:00
abstract::Photodynamic therapy (PDT) is an emerging theranostic modality for various cancers and diseases. The focus of this study was the development of tumor-targeting albumin nanoparticles containing photosensitizers for efficient PDT. To produce tumor-targeting albumin nanoparticles, the hydrophobic photosensitizer, chlorin...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno/v01p0230
更新日期:2011-04-06 00:00:00
abstract::The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.21234
更新日期:2018-01-01 00:00:00
abstract::In biology, as every science student is made to learn, ontology recapitulates phylogeny. In medicine, however, oncology recapitulates polemology, the science of warfare: The medical establishment is transitioning from highly toxic poisons that kill rapidly dividing normal and malignant cells with little specificity to...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.5658
更新日期:2013-05-25 00:00:00
abstract::Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.40664
更新日期:2020-03-04 00:00:00
abstract::Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in var...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.22952
更新日期:2018-02-07 00:00:00
abstract::Small interfering RNA (siRNA) has proved to be a powerful tool for target-specific gene silencing via RNA interference (RNAi). Its ability to control targeted gene expression gives new hope to gene therapy as a treatment for cancers and genetic diseases. However, siRNA shows poor pharmacological properties, such as lo...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.8491
更新日期:2014-09-19 00:00:00
abstract::Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-met...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.51231
更新日期:2020-10-26 00:00:00
abstract::Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.46006
更新日期:2020-10-25 00:00:00
abstract:OBJECTIVE:Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated plat...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.10020
更新日期:2015-02-05 00:00:00
abstract::[This corrects the article DOI: 10.7150/thno.21516.]. ...
journal_title:Theranostics
pub_type: 已发布勘误
doi:10.7150/thno.42847
更新日期:2020-01-18 00:00:00
abstract::Due to their tunable surface plasmon and photothermal effects, gold nanorods (AuNRs) have proved to be promising in a wide range of biomedical applications such as imaging, hyperthermia therapy and drug delivery. All these applications can be remotely controlled by near infrared (NIR) light which can penetrate deep in...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.5409
更新日期:2013-01-01 00:00:00
abstract::This article aims at alerting scientists working with nanoparticles or microparticles about the specific adverse reactions due to the intravascular pulmonary macrophages present in pigs and other cloven-hoof animals, but not in humans. The history of a 25-year old study of an ultrasound contrast agent is used to illus...
journal_title:Theranostics
pub_type: 评论,杂志文章
doi:10.7150/thno.22420
更新日期:2017-10-23 00:00:00
abstract::Aims: Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates press...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.48153
更新日期:2021-01-01 00:00:00