PHARMACOLOGICAL RESEARCH
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2022
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IF 10.334
Xiaona Xie,Xueding Cai,Feng Zhou,Yaozhe Li,Qianzi Liu,Luqiong Cai,Wenjing Zhu,Jinqiu Wei,Chenying Jin,Zitian Liu,Chunhui Jiang,Haiyang Zhao,Lehe Yang,Chengguang Zhao,Xiaoying Huang
Lung adenocarcinoma (LUAD) is associated with poor prognosis. Identifying novel cancer targets and helpful therapeutic strategies remains a serious clinical challenge. This study detected differentially expressed genes in The Cancer Genome Atlas (TCGA) LUAD data collection. We also identified a predictive DNA biomarker, G protein-coupled receptor 37 (GPR37), which was verified as a prognostic biomarker with a critical role in tumor progression. In human LUAD specimens and microarray analyses, we determined that GPR37 was significantly upregulated and associated with a poor prognosis. GPR37 downregulation markedly inhibited the proliferation and migration of LUAD both in vitro and in vivo . Mechanistically, GPR37 could bind to CDK6, thereby facilitating tumor progression in LUAD by inducing cell cycle arrest at the G1 phase. GPR37 also facilitates tumorigenesis in xenograft tumors in vivo . High-throughput screening for GPR37-targeted drugs was performed using the Natural Products Library, which revealed the potential of Hypocrellin B to inhibit GPR37 and cell growth in LUAD. We demonstrated that Hypocrellin B suppressed LUAD cell proliferation and migration both in vitro and in vivo via GPR37 inhibition. Collectively, our findings reveal the role of GPR37 in LUAD progression and migration and the potential of GPR37 as a target for the treatment of LUAD. Thus, the specific inhibition of GPR37 by the natural product Hypocrellin B may possess the potential for the treatment of LUAD.
研究领域:
肿瘤学
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分子生物学
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药理学
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癌症遗传学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Hanhan Xie,Ji Yang,Tong Liu,Xinyue Zhang,Shan Zuo,Yingjie Gao,Xi Kuang,Tao Zhang
Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.
研究领域:
胃肠病学
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药理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
NEURON
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2026
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IF 16.9
Xuemei Liu,Shuaiyu Wang,Juan Lai,Xiang Gao,Lina Wang,Bo Feng,Liang Yang,Zhengjiang Qian,Ruotian Jiang,Jun Chu,Liming Tan,Xiang Li,Liping Wang
Rapid escape from visual threats is essential for survival, yet the mechanisms establishing its “permissive state” remain poorly understood. Here, we demonstrate that osteocalcin (OCN), a bone-derived hormone, permits rapid visual escape by enhancing the excitability of a ventral tegmental area (VTA) GABAergic neuron subpopulation through the OCN-G Protein-Coupled Receptor 37 (GPR37)-cAMP-TWIK-related halothane-inhibited potassium channel (THIK-1) pathway. Loss of OCN, loss of its receptor GPR37, or conditional deletion of GPR37 in VTA GABAergic or glutamatergic neurons delays escape responses, while reconstituting OCN-GPR37 signaling in the VTA restores normal behavior. Single-cell transcriptomics and electrophysiology reveal that OCN suppresses THIK-1 potassium currents via GPR37-mediated cyclic AMP (cAMP) reduction, thereby increasing neuronal excitability. These findings reveal a novel mechanism through which a bone-derived hormone modulates the excitability of co-releasing neurons to facilitate rapid escape, offering new insights into the regulation of survival behaviors by the bone-brain metabolic axis.
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产品关联
DOI
PubMed
高影响因子
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