RNA-binding protein YBX1 promotes Type H vessels dependent bone formation in an m5C-dependent manner DOI Open Access

Yu-Jue Li,

Qi Guo,

Wen-Feng Xiao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 21, 2023

Abstract RNA Binding Proteins (RBPs) interact with and ubiquitously regulating transcripts during their life cycle. Previous works showed that RBPs play fundamental roles in the progression of angiogenesis-related diseases. However, role skeletal endothelium-dependent bone formation osteogenesis is unclear. Here, we show RBP-Ybx1 was strongly reduced vasculature from ovariectomy-induced osteoporotic mice. Endothelial cell-specific deletion Ybx1 impaired CD31 hi EMCN endothelium morphology resulted low mass, while its overexpression promoted angiogenesis-dependent ameliorated loss OVX Mechanistically, disrupted CD31, BMP4 stability an m5C-dependent manner blocked endothelial-derived release, thereby inhibiting osteogenic differentiation BMSCs. Administration recombinant protein BMSCs restored iΔEC Finally, tail vein injection CD31-modified PEG-PLGA carrying sciadopitysin, a natural agonist, pharmacologically partially reversed vessels decline improved restoration mass both aging animals. These findings demonstrated provided novel therapeutic approach for ameliorating aging-related postmenopausal osteoporosis.

Language: Английский

RNA granules: functional compartments or incidental condensates? DOI Open Access
Andrea Putnam, Laura Thomas, Géraldine Seydoux

et al.

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 354 - 376

Published: May 1, 2023

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. contain factors for biogenesis and turnover often assumed to represent specialized compartments biochemistry. Recent evidence suggests assemble by phase separation subsoluble ribonucleoprotein (RNP) complexes partially demix from cytoplasm or nucleoplasm. We explore possibility some nonessential condensation by-products arise when RNP exceed their solubility limit as a consequence cellular activity, stress, aging. describe use evolutionary mutational analyses single-molecule techniques distinguish functional "incidental condensates."

Language: Английский

Citations

57
RNA-binding proteins in cardiovascular biology and disease: the beat goes on DOI
Mirko Völkers, Thomas Preiß, Matthias W. Hentze

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(6), P. 361 - 378

Published: Jan. 2, 2024

Language: Английский

Citations

14
Targeting the “tumor microenvironment”: RNA-binding proteins in the spotlight in colorectal cancer therapy DOI
Yiwei Zhang, Yujun Zhang, Jingjing Song

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111876 - 111876

Published: March 16, 2024

Language: Английский

Citations

9
The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy DOI Creative Commons

Monica Cattaneo,

Antonio Paolo Beltrami, Anita C. Thomas

et al.

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 119(7), P. 1583 - 1595

Published: Jan. 11, 2023

Abstract Aims The ageing heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favourable gene–environment interaction. We have previously shown carriers longevity-associated variant (LAV) BPIFB4 gene enjoy prolonged spans lesser cardiovascular complications. Moreover, supplementation LAV-BPIFB4 via an adeno-associated viral vector improves performance limb ischaemia, atherosclerosis, diabetes models. Here, we asked whether could address unmet therapeutic need delay heart’s spontaneous ageing. Methods results Immunohistological studies showed remarkable reduction vessel coverage by pericytes failing hearts explanted from elderly patients. This defect was attenuated patients carrying homozygous genotype. isolated older low levels BPIFB4, depressed pro-angiogenic activity, loss ribosome biogenesis. restored pericyte pericyte-endothelial cell interactions through mechanism involving nucleolar protein nucleolin. Conversely, silencing normal mimed failure pericytes. Finally, therapy with prevented cardiac deterioration middle-aged mice rescued myocardial improving microvasculature density coverage. Conclusions report success gene/protein homeostatic processes These findings open using reverse people.

Language: Английский

Citations

18
Bioinspired cellular membrane-derived vesicles for mRNA delivery DOI Creative Commons
Xiaomin Xu, Limei Xu,

Jingzhi Wang

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(8), P. 3246 - 3266

Published: Jan. 1, 2024

The rapid advancement of mRNA as vaccines and therapeutic agents in the biomedical field has sparked hope fight against untreatable diseases.Successful clinical application therapeutics largely depends on carriers.Recently, a new exciting focus emerged natural cell-derived vesicles.These nanovesicles offer many functions, including enhanced drug delivery capabilities immune evasion, thereby presenting unique promising platform for effective safe therapeutics.In this study, we summarize characteristics properties biomimetic systems particular, discuss features cellular membrane-derived vesicles (CDVs) combination synthetic with CDVs.

Language: Английский

Citations

7
YBX1 promotes type H vessel–dependent bone formation in an m5C-dependent manner DOI Creative Commons
Yujue Li, Qi Guo,

Mingsheng Ye

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(4)

Published: Jan. 11, 2024

RNA-binding proteins (RBPs) interact with RNA and ubiquitously regulate transcripts during their life cycle, playing a fundamental role in the progression of angiogenesis-related diseases. In skeletal system, endothelium-dependent angiogenesis is indispensable for bone formation. However, RBPs formation unclear. Here, we show that RBP-Y-box-binding protein 1 (YBX1) was strongly reduced vasculature ovariectomy (OVX) mice. Endothelial cell-specific deletion Ybx1 impaired CD31-high, endomucin-high (CD31hiEMCNhi) endothelium morphology resulted low mass whereas overexpression promoted angiogenesis-dependent osteogenesis ameliorated loss. Mechanistically, YBX1 disrupted CD31, EMCN, morphogenetic 4 (BMP4) stability an m5C-dependent manner blocked endothelium-derived BMP4 release, thereby inhibiting osteogenic differentiation mesenchymal stromal cells. Administration recombinant restored Tail vein injection CD31-modified polyethylene glycol-poly (lactic-co-glycolic acid) carrying sciadopitysin, natural agonist, pharmacologically partially reversed CD31hiEMCNhi vessels' decline improved both OVX aging animals. These findings demonstrated RBP-YBX1 provided therapeutic approach ameliorating osteoporosis.

Language: Английский

Citations

6
RNA binding proteins in senescence: A potential common linker for age-related diseases? DOI
Angelica Varesi, Lucrezia Irene Maria Campagnoli, Annalisa Barbieri

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 88, P. 101958 - 101958

Published: May 20, 2023

Language: Английский

Citations

12
Role of RNA binding proteins of the Drosophila behavior and human splicing (DBHS) family in health and cancer DOI Creative Commons

Toshihiko Takeiwa,

Kazuhiro Ikeda,

Kuniko Horie

et al.

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 1 - 17

Published: March 29, 2024

RNA-binding proteins (RBPs) play crucial roles in the functions and homoeostasis of various tissues by regulating multiple events RNA processing including splicing, intracellular transport, mRNA translation. The Drosophila behavior human splicing (DBHS) family PSF/SFPQ, NONO, PSPC1 are ubiquitously expressed RBPs that contribute to physiology several tissues. In mammals, DBHS have been reported neurological diseases cancers, such as prostate, breast, liver cancer-specific gene expression. Notably, recent years, small molecules targeting developed for application cancer therapeutics. This review provides a overview pathophysiology, discusses promising diagnostic therapeutic targets cancers.

Language: Английский

Citations

4
Peptides based on the interface of hnRNPA2B1-transthyretin complex repress retinal angiogenesis in diabetic retinopathy DOI Creative Commons
Yixiu Chen, Lu Ye, Steve W. Cui

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 19, 2025

Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) plays a vital role in angiogenesis, when its nucleic acid-binding domain is occupied by transthyretin (TTR), the neovascularization of human retinal microvascular endothelial cells (hRECs) repressed under hyperglycemic conditions. HnRNPA2B1-targeting peptides (THIPs) were designed based on core fragments at TTR-hnRNPA2B1 interface. Biacore, Langmuir equilibrium adsorption, and co-immunoprecipitation (co-IP) assays performed to determine association between THIPs hnRNPA2B1. Proliferation DNA synthesis hRECs detected using CCK-8 EdU assays. Transwell, wound healing, tube formation used evaluate migratory angiogenic capacity hRECs. Related RNA protein expression levels tested quantitative PCR western blot assays, respectively. Streptozotocin (STZ)-induced diabetic retinopathy (DR) model rats intravitreally injected with 5 μL AAV9 virus (1 × 1012 vg/mL) every 8 weeks, sterile saline as control. After 16 retinas extracted subjected Evans blue leakage trypsin digestion Retinal paraffin sections prepared stained hematoxylin eosin (H&E) or immunohistochemical immunofluorescence co-IP analyses demonstrated that four specifically recognized labeling showed inhibited proliferation hyperglycemia. healing Quantitative suggested exerted their effects via STAT4/miR-223-3p/FBXW7 downstream Notch1/Akt/mTOR axes. In vivo studies DR rat revealed intravitreal administration THIP-4 significantly mitigated leakage, capillary decellularization, pericyte loss, fibrosis, gliosis during progression. Our findings hyperglycemia, suppressed progression axes both vitro vivo. These results indicated has strong potential for clinical application other angiogenesis associated diseases.

Language: Английский

Citations

0
Value of Bioinformatics Models for Predicting Translational Control of Angiogenesis DOI
Michal Shaposhnikov, Juilee Thakar, Bradford C. Berk

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: 136(10), P. 1147 - 1165

Published: May 8, 2025

Angiogenesis, the formation of new blood vessels, is a fundamental biological process with implications for both physiological functions and pathological conditions. While transcriptional regulation angiogenesis, mediated by factors such as HIF-1α (hypoxia-inducible factor 1-alpha) VEGF (vascular endothelial growth factor), well-characterized, translational this remains underexplored. Bioinformatics has emerged an indispensable tool advancing our understanding regulation, offering predictive models that leverage large data sets to guide research optimize experimental approaches. However, significant gap persists between bioinformatics experts other researchers, limiting accessibility utility these tools in broader scientific community. To address divide, user-friendly platforms are being developed democratize access analytics empower researchers across disciplines. Translational control, compared offers more energy-efficient mechanism facilitates rapid cellular responses environmental changes. Furthermore, regulators themselves often subject emphasizing interconnected nature regulatory layers. Investigating requires advanced, accessible analyze RNA structures, interacting micro-RNAs, long noncoding RNAs, RBPs (RNA-binding proteins). Predictive structure, human internal ribosome entry site Atlas, RBPSuite enable study motifs RNA-protein interactions, shedding light on critical mechanisms. This review highlights transformative role using widely Web-browser interface elucidate angiogenesis. The discussed extend beyond applications diverse fields, including clinical care. By integrating insights, can streamline hypothesis generation, reduce costs, find novel regulators. bridging knowledge gap, aims worldwide adopt their work, fostering innovation accelerating discovery.

Language: Английский

Citations

0