- Angiogenesis and VEGF in Cancer
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Immune cells in cancer
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Axon Guidance and Neuronal Signaling
- Lymphatic System and Diseases
- Neurogenesis and neuroplasticity mechanisms
- Caveolin-1 and cellular processes
- Nerve injury and regeneration
- Platelet Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
- Biomarkers in Disease Mechanisms
- Lipid metabolism and disorders
- Retinal and Macular Surgery
- Glioma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Cell death mechanisms and regulation
- Proteoglycans and glycosaminoglycans research
- Ubiquitin and proteasome pathways
- Circular RNAs in diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nuclear Receptors and Signaling
The Fourth People's Hospital
2024
Fourth People’s Hospital of Jinan
2024
Sun Yat-sen University
2012-2023
Beijing Chaoyang Emergency Medical Center
2023
National Eye Institute
2007-2013
Children's Cancer and Blood Foundation
2013
Neurological Surgery
2013
Memorial Sloan Kettering Cancer Center
2013
Cornell University
2013
National Institutes of Health
2007-2012
VEGF-B, a homolog of VEGF discovered long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it received little attention from the field. In this study, using different animal models and multiple types vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, critical their survival. Importantly, survival effect only on endothelial but also pericytes, smooth muscle stem/progenitor cells. vivo, targeting inhibited both...
Rationale: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function platelets in pathologies is thus far poorly defined. Objective: We addressed role mediating CNS inflammation EAE. Methods Results: found that were present human MS lesions as well mice subjected to EAE but not from control nondiseased mice. Platelet depletion at effector-inflammatory phase resulted significantly...
Despite its early discovery and high sequence homology to the other VEGF family members, biological functions of VEGF-B remain poorly understood. We revealed here a novel function for as potent inhibitor apoptosis. Using gene expression profiling mouse primary aortic smooth muscle cells, confirming results by real-time PCR using rat cell lines, we showed that inhibited genes encoding proapoptotic BH3-only proteins apoptosis- death–related proteins, including p53 members caspase family, via...
Platelet-derived growth factor CC (PDGF-CC) is the third member of PDGF family discovered after more than two decades studies on original members family, PDGF-AA and PDGF-BB. The biological function PDGF-CC remains largely to be explored. We report a novel finding that potent neuroprotective acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models neuronal injury, such as axotomy-induced death, neurotoxin-induced 6-hydroxydopamine–induced...
Abstract Improved vaccination requires better delivery of antigens and activation the natural immune response. Here we report a lipid nanoparticle system with capacity to carry antigens, including mRNA proteins, which is formed into virus-like structure by surface decoration spike demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on deliver XBB.1. particle enables specific augmentation mRNAs expressed in human respiratory epithelial cells...
The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result the emerging drug resistance to anti-VEGF therapies. PDGF-CC third member PDGF family discovered after more than two decades studies on PDGF-AA and PDGF-BB. biological function underlying cellular molecular mechanisms remain largely unexplored. Here, using different animal models, we report that inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed...
VEGF is believed to be a master regulator in both developmental and pathological angiogenesis.The role of PDGF-C angiogenesis, however, only at the beginning being revealed.We others have shown that critical player angiogenesis because its pleiotropic effects on multiple cellular targets.The angiogenic pathways induced by are, large extent, VEGF-independent.These may include, but not limited to, direct effect vascular cells, tissue stroma fibroblasts, macrophages.Taken together, pleiotropic,...
Enhanced platelet-derived growth factor (PDGF) signaling in glioma drives its development and progression. In this study, we define a unique role for stroma-derived PDGF maintaining tumor homeostasis within the microenvironment. Large numbers of receptor-α (PDGFRα)-expressing stromal cells derived from oligodendrocytes progenitor (OPC) were discovered at invasive front high-grade gliomas, which they exhibited perivascular distribution. PDGFRα-deficient host mice, orthotopic Gl261 tumors...
Significance Despite being discovered a long time ago, the functional properties of VEGF-B remain poorly understood. However, several clinical treatments use drugs that target and other VEGF family members. It is therefore crucial to gain deeper insights into function underlying mechanisms. Here, we found has potent antioxidative functions, making it member show such property. We further identified critical downstream effector VEGF-B, Gpx1, through which protects against retinal...
The constant mutation of SARS-CoV-2 has led to the continuous appearance viral variants and their pandemics improved development vaccines with a broad spectrum antigens curb spread virus. work described here suggested novel vaccine virus-like structure (VLS) composed combined mRNA protein that is capable stimulating immune system in manner similar infection. This VLS characterized by its ability specifically target dendritic cells and/or macrophages through S1 recognition DC-SIGN receptor...
Group III presynaptic metabotropic glutamate receptors (mGluRs) play a central role in regulating activity through G-protein effects on ion channels and signal transducing enzymes. Like all Class C G-protein-coupled receptors, mGluR8 has an extended intracellular C-terminal domain (CTD) presumed to allow for modulation of downstream signaling. In yeast two-hybrid screen adult rat brain cDNA library with the CTDs mGluR8a 8b (mGluR8-C) as baits, we identified sumo1 four different components...
Injury to the optic nerve can lead axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples such diseases human include traumatic neuropathy and degeneration glaucoma. It is characterized typical changes head, progressive loss cells, if uncontrolled, leading blindness. The crush (ONC) injury mouse model an important experimental disease for neuropathy, glaucoma, etc. In this model, leads apoptosis. This be used...
Significance Caveolin-1 (Cav-1) is a major structural protein of caveolae found in cell membranes and critical for numerous cellular functions. However, it remains unclear whether Cav-1 plays role ocular neovascularization, cause blindness. In this study, we that the gene deletion exacerbates cavtratin, permeable peptide mimicking function, inhibits neovascularization by targeting multiple components angiogenesis. Importantly, combined administration cavtratin anti–VEGF-A more effectively,...
Retinal ganglion cells (RGCs) apoptosis and their axon degeneration are pivotal features in glaucoma. Previous studies suggest that the process of RGCs soma is distinct from both them lead to vision loss but separately. However, since a normal visual function relies on integrity axon, synapse retina, comprehensive understanding changes these neuron components glaucoma desired. Therefore, an acute ocular hypertension (AOH) model mice, we systematically evaluated retinal soma, alteration at...
Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role PDGF-DD in pathological angiogenesis and underlying cellular molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that expression was up-regulated during angiogenesis, inhibition suppressed both choroidal retinal neovascularization. We also demonstrated novel mechanism mediating function PDGF-DD. induced glycogen synthase kinase-3β...
The p53 upregulated modulator of apoptosis (PUMA) is known as an essential inducer. Here, we report the seemingly paradoxical finding that PUMA a proangiogenic factor critically required for proliferation and survival vascular microglia cells. Strikingly, Puma deficiency by genetic deletion or small hairpin RNA knockdown inhibited developmental pathological angiogenesis reduced numbers in vivo, whereas gene delivery increased cell survival. Mechanistically, revealed plays critical role...
Abstract Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago. However, its role in hyperglycemia- and VEGF-A inhibition-induced retinal apoptosis remains unknown thus far. Yet, drugs that can block VEGF-B are being used to treat patients with diabetic retinopathy other ocular neovascular diseases. It is therefore urgent have better understanding of the function these pathologies. Here, we report both streptozotocin (STZ)-induced diabetes rats Macugen intravitreal...
Abstract Apomorphine, the catechol‐derived dopamine D 1 /D 2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of enzyme tyrosine hydroxylase, a marker for DA neurons, fetal rat cerebrocortical cultures whilst presence brain‐derived neurotrophic factor. The present study demonstrated treatment ventral mesencephalic with caused marked increase number dopaminergic neurons. action can be mimicked by...
Significance PDGF-CC plays critical roles in many biological processes, such as development, tumor growth, and angiogenesis. However, its role blood vessel survival/regression the underlying mechanisms remain unknown. Here, using different loss- gain-of-function assays multiple model systems, we show that is a vascular protective factor required to maintain survival. Mechanistically, found heme oxygenase-1 (HMOX1) activity crucial for protective/survival effect of PDGF-CC. Given general...