Dataset Information

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

ABSTRACT: Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5?mM and 5?mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5?mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.

SUBMITTER: Xiao X

PROVIDER: S-EPMC7700023 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

Xiao Xiaoqiang X Chen Min M Xu Yanxuan Y Huang Shaofen S Liang Jiajian J Cao Yingjie Y Chen Haoyu H

Oxidative medicine and cellular longevity 20201120

Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. ...[more]

PMID: 33274003

Similar Datasets

Project description:BackgroundBreast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear.MethodsThe prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model.ResultsACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs.ConclusionsOur findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway.Trial registrationRetrospectively registered.

Project description:BackgroundButyrate acts as a regulator in multiple inflammatory organ injuries. However, the role of butyrate in acute liver injury has not yet been fully explored. In the present study, we aimed to investigate the association between butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the signaling pathways involved.MethodsLPS-induced acute liver injury was induced by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver injury was detected by serum markers, tissue morphology, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). Cell models were first treated with sodium butyrate (4 μmol/mL), followed by LPS (1 μg/mL) half an hour later in GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB)-element levels including TLR4, TRAF6, IKKβ, IкBα, phospho-IкBα, p65, and phospho-p65 by Western blot. The interaction between GPR43 and β-arrestin-2 was tested by co-immunoprecipitation.ResultsSodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium butyrate downregulated some elements of the TLR4/NF-κB pathway, including phospho-IκBα and phospho-p65, in RAW264.7 cells. Increased interactions between GPR43 and β-arrestin-2, and between β-arrestin-2 and IкBα were observed.ConclusionSodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/β-arrestin-2/NF-κB signaling pathway.

Dataset Information

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

Publications

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets