更新于：2024-11-01

OSGIN1

更新于：2024-11-01

基本信息

别名

BDGI、BMSC-derived growth inhibitor、Bone marrow stromal cell-derived growth inhibitor

+ [7]

简介

Regulates the differentiation and proliferation through the regulation of cell death.

关联

项与 OSGIN1 相关的药物

GIF-2651X-G1

靶点

OSGIN1

作用机制

OSGIN1抑制剂

在研机构

Nagoya University [+1]

原研机构

Gifu University

在研适应症

神经系统变性病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 OSGIN1 相关的临床结果

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100 项与 OSGIN1 相关的转化医学

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0 项与 OSGIN1 相关的专利（医药）

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项与 OSGIN1 相关的文献（医药）

2024-11-01·Toxicology Letters

OSGIN1 regulates PM2.5-induced fibrosis via mediating autophagy in an in vitro model of COPD

Article

作者: Tang, Xiying ; Zhu, Huanhuan ; Yuan, Qi ; Xiao, Qi ; Zhang, Huilin ; Zhang, Zhengdong ; Zhou, Meiyu ; Chu, Haiyan ; Sun, Guanting

Fine particulate matter (PM_2.5) has been identified as a significant contributing factor to the exacerbation of chronic obstructive pulmonary disease (COPD). It has been observed that PM_2.5 may induce lung fibrosis in COPD, although the precise molecular mechanism behind this remains unclear. In a previous study, we demonstrated that PM_2.5 upregulates oxidative stress induced growth inhibitor 1 (OSGIN1), which in turn leads to injury in airway epithelial cells, thereby, suggesting a potential link between PM_2.5 exposure and COPD. Based on this, we hypothesized that OSGIN1 plays a role in PM_2.5-induced fibrosis in COPD. Human bronchial epithelial cells (HBEs) were treated with cigarette smoke extract (CSE) to construct an in vitro model of COPD. Our findings revealed that PM_2.5 increased fibrosis indicators and upregulated OSGIN1 in CSE-stimulated HBEs (CSE-HBEs), and knockdown of OSGIN1 reduced the expression of fibrosis indicators. Through the use of microRNA target prediction software and the Gene Expression Omnibus database, we predicted miRNAs that targeted OSGIN1 in COPD. Subsequently, real-time polymerase chain reaction and western blot analysis confirmed that PM_2.5 modulated miR-654-5p to regulate OSGIN1 in CSE-HBEs. Western blot demonstrated that OSGIN1 induced autophagy, thereby exacerbating fibrosis in CSE-HBEs. In summary, our results suggest that PM_2.5 upregulates OSGIN1 through inhibiting miR-654-5p, leading to increased autophagy and fibrosis in CSE-HBEs.

2024-05-29·Oncogene

NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells

Article

作者: Salvini, Laura ; Chiariello, Mario ; Giustarini, Daniela ; Giurisato, Emanuele ; Catona, Orazio ; D'Aurizio, Romina ; Galvagni, Federico ; Pio, Elena ; Bottoni, Laura ; Rossi, Ranieri ; Neri, Francesco ; Rasa, Mahdi ; Rocchio, Chiara ; Minetti, Alberto ; Realini, Giulia ; Franci, Lorenzo ; Orlandini, Maurizio

AbstractTriple-negative breast cancer (TNBC) is a very aggressive and heterogeneous group of tumors. In order to develop effective therapeutic strategies, it is therefore essential to identify the subtype-specific molecular mechanisms underlying disease progression and resistance to chemotherapy. TNBC cells are highly dependent on exogenous cystine, provided by overexpression of the cystine/glutamate antiporter SLC7A11/xCT, to fuel glutathione synthesis and promote an oxidative stress response consistent with their high metabolic demands. Here we show that TNBC cells of the mesenchymal stem-like subtype (MSL) utilize forced cystine uptake to induce activation of the transcription factor NRF2 and promote a glutathione-independent mechanism to defend against oxidative stress. Mechanistically, we demonstrate that NRF2 activation is mediated by direct cysteinylation of the inhibitor KEAP1. Furthermore, we show that cystine-mediated NRF2 activation induces the expression of important genes involved in oxidative stress response, but also in epithelial-to-mesenchymal transition and stem-like phenotype. Remarkably, in survival analysis, four upregulated genes (OSGIN1, RGS17, SRXN1, AKR1B10) are negative prognostic markers for TNBC. Finally, expression of exogenous OSGIN1, similarly to expression of exogenous NRF2, can prevent cystine depletion-dependent death of MSL TNBC cells. The results suggest that the cystine/NRF2/OSGIN1 axis is a potential target for effective treatment of MSL TNBCs.

2024-03-12·Proceedings of the National Academy of Sciences1区 · 综合性期刊

OSGN-1 is a conserved flavin-containing monooxygenase required to stabilize the intercellular bridge in late cytokinesis

1区 · 综合性期刊

Article

作者: Lacroix, Léa ; Saba-El-Leil, Marc K. ; Brière, Jonathan ; Goupil, Eugénie ; Guga, Sandra ; Labbé, Jean-Claude ; Meloche, Sylvain

Cytokinesis is the last step of cell division and is regulated by the small GTPase RhoA. RhoA activity is required for all steps of cytokinesis, including prior to abscission when daughter cells are ultimately physically separated. Like germ cells in all animals, the Caenorhabditis elegans embryonic germline founder cell initiates cytokinesis but does not complete abscission, leaving a stable intercellular bridge between the two daughter cells. Here, we identify and characterize C. elegans OSGN-1 as a cytokinetic regulator that promotes RhoA activity during late cytokinesis. Sequence analyses and biochemical reconstitutions reveal that OSGN-1 is a flavin-containing monooxygenase (MO). Genetic analyses indicate that the MO activity of OSGN-1 is required to maintain active RhoA at the end of cytokinesis in the germline founder cell and to stabilize the intercellular bridge. Deletion of OSGIN1 in human cells results in an increase in binucleation as a result of cytokinetic furrow regression, and this phenotype can be rescued by expressing a catalytically active form of C. elegans OSGN-1, indicating that OSGN-1 and OSGIN1 are functional orthologs. We propose that OSGN-1 and OSGIN1 are conserved MO enzymes required to maintain RhoA activity at the intercellular bridge during late cytokinesis and thus favor its stability, enabling proper abscission in human cells and bridge stabilization in C. elegans germ cells.