更新于：2024-09-19

ITGB8

更新于：2024-09-19

基本信息

别名

Integrin beta-8、integrin subunit beta 8、integrin, beta 8

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简介

Integrin alpha-V:beta-8 (ITGAV:ITGB8) is a receptor for fibronectin (PubMed:1918072). It recognizes the sequence R-G-D in its ligands (PubMed:1918072). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs) (Probable). Required during vasculogenesis (By similarity).

关联

项与 ITGB8 相关的药物

MEDI-8367

靶点

ITGB8

作用机制

ITGB8抑制剂

在研机构-

原研机构

AstraZeneca PLC

在研适应症-

非在研适应症

慢性肾病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 ITGB8 相关的临床试验

NCT04365218 / Completed临床1期

A Phase I Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of MEDI8367 Administered as Single Ascending Doses in Healthy Subjects, and as a Single Dose in Healthy Subjects of Japanese-descent and in Subjects With Chronic Kidney Disease

This Phase I First in Human (FIH) study is being conducted to determine the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity profile of MEDI8367 across the dose range.

开始日期2020-07-22

申办/合作机构

AstraZeneca PLC

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100 项与 ITGB8 相关的临床结果

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100 项与 ITGB8 相关的转化医学

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0 项与 ITGB8 相关的专利（医药）

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191

项与 ITGB8 相关的文献（医药）

2024-11-01·Endocrine, Metabolic & Immune Disorders - Drug Targets

Single-Cell RNA Sequencing Reveals Transcriptional Signatures and Cell-Cell Communication in Diabetic Retinopathy

Article

作者: Pang, Lin ; Li, Junhong ; Li, Muye ; Wang, Lin ; Peng, Yueling

Background::Diabetic retinopathy (DR) is a major cause of vision loss in workingage individuals worldwide. Cell-to-cell communication between retinal cells and retinal pigment epithelial cells (RPEs) in DR is still unclear, so this study aimed to generate a single-cell atlas and identify receptor‒ligand communication between retinal cells and RPEs.Methods::A mouse single-cell RNA sequencing (scRNA-seq) dataset was retrieved from the GEO database (GSE178121) and was further analyzed with the R package Seurat. Cell cluster annotation was performed to further analyze cell‒cell communication. The differentially expressed genes (DEGs) in RPEs were explored through pathway enrichment analysis and the protein‒ protein interaction (PPI) network. Core genes in the PPI were verified by quantitative PCR in ARPE-19 cells.Results::We observed an increased proportion of RPEs in STZ mice. Although some overall intercellular communication pathways did not differ significantly in the STZ and control groups, RPEs relayed significantly more signals in the STZ group. In addition, THBS1, ITGB1, COL9A3, ITGB8, VTN, TIMP2, and FBN1 were found to be the core DEGs of the PPI network in RPEs. qPCR results showed that the expression of ITGB1, COL9A3, ITGB8, VTN, TIMP2, and FBN1 was higher and consistent with scRNA-seq results in ARPE-19 cells under hyperglycemic conditions.Conclusion::Our study, for the first time, investigated how signals that RPEs relay to and from other cells underly the progression of DR based on scRNA-seq. These signaling pathways and hub genes may provide new insights into DR mechanisms and therapeutic targets.

2024-09-01·Gene

Preliminary study on the mechanism by which exosomes derived from human exfoliated deciduous teeth improve the proliferation and osteogenic inhibitory effect of glucocorticoid-induced BMSCs

Article

作者: Lu, Yang ; Wang, Xinmin ; Xu, Jie ; Lv, Jian ; Bai, Yuxi ; Liu, Fei

BACKGROUNDSteroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by a collapsed femoral head caused by the overuse of glucocorticoids. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) is an important pathological feature of SONFH. In this study, we investigated whether exosomes from SHEDs (stem cells from human exfoliated deciduous teeth) have a therapeutic effect on glucocorticoid-induced inhibition of proliferation and osteogenesis in BMSCs, and elucidated the underlying mechanisms involved.METHODSPrimary dental pulp cells were isolated and cultured from human deciduous tooth pulp, SHEDs were isolated and purified by the limiting dilution method and exosomes were isolated from the supernatants of SHEDs by ultracentrifugation. The cell surface markers CD31, CD34, CD45, CD73, CD90 and CD105 were detected by flow cytometry. A Cell-Counting-Kit-8 assay was used to detect cell activity. ALP and Alizarin Red staining were used to identify osteogenic differentiation ability, and exosomes were identified using transmission electron microscopy, NanoFCM and Western blotting. PKH67 fluorescence was used to track the uptake of exosomes by BMSCs. Transcriptome analysis combined with quantitative real-time PCR was used to explore the underlying mechanism involved.RESULTSExosomes secreted by SHEDs can be endocytosed by BMSCs, and can partially reverse the inhibitory effects of glucocorticoids on the viability and osteogenic differentiation of BMSCs. Transcriptome sequencing analysis revealed that the differentially expressed mRNAs regulated by SHED-derived exosomes were enriched mainly in signaling pathways such as the apoptosis pathway, the PI3K-Akt signaling pathway, the Hippo signaling pathway and the p53 signaling pathway. qPCR showed that SHED-derived exosomes reversed the dexamethasone-induced upregulation of HGF and ITGB8 expression and the inhibition of EFNA1 expression, but further increased the dexamethasone-induced downregulation of IL7 expression. In conclusion, SHED-derived exosomes partially reversed the inhibitory effects of glucocorticoids on BMSC proliferation and osteogenesis by inhibiting the expression of HGF, ITGB8 and IL7, and upregulating the expression of EFNA1.

2024-08-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms

Article

作者: Huang, Qinghai ; Wu, Yina ; Li, Siqi ; Lu, Zhiwen ; Zhu, Shijie ; Xu, Xiaolong

BACKGROUNDThe dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear.METHODScircRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms.RESULTSBoth hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-β-mediated signaling pathway were significantly enhanced.CONCLUSIONThe hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.