Dataset Information

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

ABSTRACT: Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

SUBMITTER: Zhou ZY

PROVIDER: S-EPMC10300109 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Zhou Zi-Yi ZY Chang Tian-Fang TF Lin Zhi-Bin ZB Jing Yu-Tong YT Wen Li-Shi LS Niu Ya-Li YL Bai Qian Q Guo Chang-Mei CM Sun Jia-Xing JX Wang Yu-Sheng YS Dou Guo-Rui GR

Cell death & disease 20230628 6

Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathwa ...[more]

PMID: 37369647

Similar Datasets

Project description:RationaleThe highly conserved NOTCH (neurogenic locus notch homolog protein) signaling pathway functions as a key cell-cell interaction mechanism controlling cell fate and tissue patterning, whereas its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders.ObjectiveThe aim of this study was to investigate the role of SUMOylation in endothelial NOTCH signaling and angiogenesis.Methods and resultsEndothelial SENP1 (sentrin-specific protease 1) deletion, in newly generated endothelial SENP1 (the major protease of the SUMO system)-deficient mice, significantly delayed retinal vascularization by maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and immunoprecipitation analyses and dual-luciferase assays of natural and SUMO-conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized it for translocation to the nucleus where it functions as a cotranscriptional factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn suppressed VEGF (vascular endothelial growth factor) receptor signaling and angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro angiogenesis assays.ConclusionsThese results establish reversible NOTCH1 SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic signaling; SENP1 acts as a critical intrinsic mediator of this process. These findings may apply to NOTCH-regulated biological events in nonvascular tissues and provide a novel therapeutic strategy for vascular diseases and tumors.

Dataset Information

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Publications

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets