VEGFR1
- Known as:
- VEGFR1
- Catalog number:
- MA1101
- Product Quantity:
- 100μg
- Category:
- -
- Supplier:
- SDlabs
- Gene target:
- VEGFR1
Related genes to: VEGFR1
- Gene:
- FLT1 NIH gene
- Name:
- fms related tyrosine kinase 1
- Previous symbol:
- FLT
- Synonyms:
- VEGFR1
- Chromosome:
- 13q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-04-23
Related products to: VEGFR1
Related articles to: VEGFR1
- Vascular aging is a critical pathological basis of cardiovascular diseases (CVDs), involving functional abnormalities of vascular smooth muscle cells (VSMCs). This study investigated whether downregulation of Fms-related tyrosine kinase 1 (FLT1) ameliorates vascular aging by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway in VSMCs. Angiotensin II (Ang II) and bleomycin (Bleo) were used to induce VSMC senescence in vitro and establish a mouse aortic aging model in vivo. FLT1 was knocked down and overexpressed using small interfering RNA (siRNA) and pcDNA3.1 vectors, respectively. In vitro, cell proliferation was assessed by the Cell Counting Kit-8 assay and the 5-Ethynyl-2'-deoxyuridine incorporation assay, while senescence was evaluated through senescence-associated β-galactosidase (SA-β-gal) staining, gamma-H2A histone family member X (γ-H2AX) immunofluorescence (to assess DNA damage), and measurements of the nicotinamide adenine dinucleotide (NAD/NADH) ratio. In vivo, vascular stiffness was assessed via pulse wave velocity (PWV), and aortic histopathology was examined using histological staining and immunohistochemistry. Additionally, Western blot analysis was performed to detect MAPK signaling pathway-related protein levels. Ang II and Bleo induced VSMC senescence in vitro (as evidenced by inhibited proliferation, increased SA-β-gal positivity, elevated DNA damage, and a reduced NAD/NADH ratio) and promoted aortic aging in mice (characterized by elevated PWV, collagen deposition, and elastin degradation). FLT1 expression was upregulated in Ang II and Bleo-induced VSMCs and mouse aortic tissues. Downregulation of FLT1 alleviated VSMC and aortic aging while suppressing key proteins of the MAPK pathway, including p-ERK1/2 and p-p38 MAPK. Moreover, MAPK pathway inhibitors attenuated the pro-senescence effects of FLT1 overexpression in VSMCs and mouse aortas. Downregulation of FLT1 ameliorates VSMC and vascular aging by inhibiting the MAPK signaling pathway. These findings indicate a new treatment approach for CVDs related to aging. - Source: PubMed
Publication date: 2026/05/26
Fu LiDuan JingFengGe MinFan YanOu YangZheng - Ovarian dysfunction resulting from metabolic or toxic injury is characterized by follicular depletion, stromal remodeling, oxidative stress, and endocrine dysregulation. Placenta-derived mesenchymal stem cells (PD-MSCs) have been proposed as a potential therapeutic approach due to their paracrine factors, including placental growth factor (PlGF). However, the pathways through which PD-MSCs exert protective effects on the ovary remain insufficiently defined. In this study, we examined whether PD-MSC transplantation ameliorates ovarian injury in a thioacetamide (TAA)-induced ovarian insufficiency model and explored the signaling events potentially associated with this response. Female rats were administered TAA for 12 weeks, and PD-MSCs were transplanted at week 8. We assessed ovarian morphology, fibrosis, oxidative stress markers, hormonal profiles, and follicle development. Complementary in vitro experiments using TAA-treated KGN granulosa-like cells were performed to investigate potential mechanistic associations. PD-MSC transplantation improved ovarian architecture, reduced collagen deposition, enhanced follicle growth, and mitigated oxidative stress. These changes were accompanied by increased PlGF expression and enhanced activation of fms-like tyrosine kinase-1 (Flt-1), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidant pathways. In vitro, PD-MSCs coculture similarly attenuated oxidative stress and partially improved mitochondrial membrane potential in damaged KGN cells. Together, these findings suggest that PD-MSCs ameliorate ovarian structural damage and oxidative stress in TAA-induced injury, potentially through paracrine mechanisms partly involving PlGF/Flt-1-associated antioxidant signaling. This work supports the therapeutic potential of PD-MSCs for metabolic or toxicant-induced ovarian insufficiency while underscoring the need for further studies to fully delineate the specific contribution of PlGF and its interaction with downstream antioxidant pathways. - Source: PubMed
Publication date: 2026/05/10
Shin Jae-YoungLee Dae-HyunPark HyeriKim Young RanKim Gi Jin - Heavy metal contamination has become an emerging global health concern, yet the promoting effects of mixed heavy metal exposure on colorectal cancer risk remains poorly understood. In this study, plasma concentrations of 25 heavy metals were obtained from an in-house elemental database comprising both colorectal cancer patients and healthy controls, and exposure concentrations were then defined based on these human plasma detection data and relevant public datasets. Machine learning algorithms and mixture exposure models were applied to identify key heavy metals associated with colorectal cancer risk. RNA-seq datasets were integrated to screen for genes exhibiting heavy metal-tumor-specific characteristics. A total of 270379 cells from 95 samples were analyzed to identify cell subsets sensitive to mixed heavy metal exposure. Molecular and cellular experiments were performed to validate the underlying mechanisms. We first identified stannum (Sn), antimony (Sb), tantalum (Ta), and thallium (Tl) as a mixture of heavy metal highly associated with colorectal cancer risk. , and were further identified as key genes linked to colorectal tumors under conditions of mixed heavy metal exposure. Based on scRNA-seq analyses, endothelial tip cells were first identified as exhibiting heightened sensitivity to mixed heavy metal exposure. Mechanistically, acute mixed heavy metal exposure upregulated VEGFA expression in colorectal tumor epithelial cells. Co-culture experiments demonstrated enhanced epithelial-endothelial communication through the VEGFA-FLT1 axis, accompanied by increased expression of ESM1 and ANGPT2 in endothelial cells. Collectively, these findings suggest that mixed heavy metal exposure promotes angiogenesis by enhancing the interaction between colorectal tumor epithelial and endothelial cells, thereby increasing the risk of colorectal cancer. This study provides a scientific basis for improving strategies to control heavy metal contamination. - Source: PubMed
Publication date: 2026/05/25
Zhang ShuoZheng YudanWang JingZhou JieyuLi ZhengyiZhou ZiyanXu ShenyaXin JunyiFu ZanGu DongyingLi ShuweiWang Meilin - Chronic periodontitis (CP) and postmenopausal osteoporosis (PMOP) are prevalent chronic inflammatory diseases characterized by bone resorption; however, the shared molecular mechanisms between them remain unclear. Hub genes associated with CP and PMOP were identified through bioinformatics analysis. Lipopolysaccharide (LPS)-stimulated MC3T3-E1 osteoblasts were used to establish an in vitro model, followed by lentiviral-mediated matrix metalloproteinase 14 (MMP14) knockdown. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. Levels of inflammatory cytokines and oxidative stress markers were measured by enzyme-linked immunosorbent assay. Intracellular ROS were detected using 2',7'-dichlorodihydrofluorescein diacetate fluorescence staining. Western blot analysis was performed to assess the expression of osteoclast-related markers. The involvement of the JAK2/STAT3 pathway was assessed using the JAK2 agonist RO8191 and inhibitor AG490. PDGFRB, MMP14, VWF, PECAM1, FLT1, and CXCR4 were identified as hub genes and were all upregulated in LPS-stimulated MC3T3-E1 osteoblasts. Silencing MMP14 improved cell viability and reduced apoptosis, inflammatory cytokine release (TNF-α, IL-1β, and IL-6), oxidative stress markers (MDA and ROS), and osteoclast-associated markers (CTX-I, TRAP, and Cathepsin K), while restoring SOD activity. Mechanistically, MMP14 silencing decreased the phosphorylation levels of JAK2 and STAT3. The protective phenotype caused by MMP14 silencing was significantly abolished by RO8191 but mimicked by treatment with AG490. MMP14 may represent a potential molecular link between CP-associated bone loss and PMOP. Modulation of the MMP14-JAK2/STAT3 signaling axis may represent a promising research direction for inflammation-related bone loss. - Source: PubMed
Jiang XiliangJia WeiqiMa QinciFan WanpengLuo Shigao - The immunosuppressive tumor microenvironment and vascular abnormalities are important factors affecting the anticancer effects of chemotherapeutic drugs. Previous studies have shown that moxibustion combined with cisplatin can improve tumor immunity and vascular normalization. The aim is to further explore the pathways and molecular mechanisms by which moxibustion combined with cisplatin exerts anti-tumor effects through regulating the tumor immune-vascular microenvironment. Through RNA sequencing and bioinformatics analysis, we identified related signaling pathways and key molecules, which were subsequently validated at both cellular and molecular levels. The combination of moxibustion and cisplatin enhanced the infiltration of CD4 T cells and myeloid dendritic cells in tumor tissues. Moreover, it elevated the M1/M2 and Th1/Th2 ratios along with enhanced Th1 cell polarization. This therapeutic approach modulated immune-related molecules through upregulation of Il2 and downregulation of Il1β at the mRNA level, accompanied by decreased protein expression of CXCL1, IL-13, CCL3, and CCL4. Furthermore, moxibustion upregulated and mRNA levels and downregulated and . Thus, the imbalance between pro-angiogenic and anti-angiogenic factors in the tumor microenvironment can be corrected. Notably, the anti-tumor effects of moxibustion combined with cisplatin were abrogated upon intratumoral injection of the IFN-γ neutralizing antibody, suggesting the critical role of IFN-γ. The findings demonstrate that the combination of moxibustion and cisplatin can enhance tumor immunity, inhibit tumor angiogenesis. This therapeutic effect is potentially mediated through the upregulation of IFN-γ. - Source: PubMed
Publication date: 2026/05/19
Lu ShanshanWang JiaqiPan YueYang YuanzhenHuang JinLi ShanshanWang BinZhao SuhongMa NingZhao JiayueHuang JingGuo YiXu Zhifang