EUROPEAN JOURNAL OF CELL BIOLOGY
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2021
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IF 4.492
Jian Zhao,Zhaoyu Liu,Zhihui Chang
Endothelial cell pyroptosis is a novel cause of endothelial dysfunction in sepsis. Reticulocalbin-2 (RCN2) is involved in regulating vascular inflammation and plays an important role in the cardiovascular system. However, the role of RCN2 in inflammation-induced endothelial cell pyroptosis remains to be explored. Here, we found that RCN2 was upregulated after lipopolysaccharide (LPS) treatment in a concentration‐ and time-dependent manner. RCN2 knockdown resulted in a significant decrease in pyroptosis, reduced LDH and IL-1β release and ROS production and inhibited the expression of pyroptosis‐related proteins (NLRP3, cleaved caspase-1, and cleaved GSDMD) (all p < 0.05). N‐acetyl‐L‐cysteine (NAC) counteracted the effects of RCN2 on pyroptosis (all p < 0.01). The silencing of RCN2 antagonized the inhibitory effect of LPS on the phosphorylation of eNOS (p < 0.05). We predicted and confirmed that specificity protein-1(SP1) could directly bind to the RCN2 promoter and regulate RCN2. RCN2 overexpression rescued the inhibitory effect of SP1 inhibitor on HUVEC pyroptosis induced by LPS (all p < 0.05). These findings suggested that the activation of the SP1/RCN2/ROS signaling pathway could promote LPS-induced endothelial cell pyroptosis.
研究领域:
免疫学
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心血管生物学
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细胞信号传导
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炎症
✓ 已验证
DOI
PubMed
高影响因子
CELL RESEARCH
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2025
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IF 25.9
Xie Ling-Qi,Hu Biao,Lu Ren-Bin,Cheng Ya-Lun,Chen Xin,Wen Jie,Xiao Yao,An Yu-Ze,Peng Ning,Dai Yu,Xie Genqing,Guo Qi,Peng Hui,Luo Xiang-Hang
Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear. Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it Raptin. Raptin release is timed by the circuit from vasopressin-expressing neurons in the suprachiasmatic nucleus to RCN2-positive neurons in the paraventricular nucleus. Raptin levels peak during sleep, which is blunted by sleep deficiency. Raptin binds to glutamate metabotropic receptor 3 (GRM3) in neurons of the hypothalamus and stomach to inhibit appetite and gastric emptying, respectively. Raptin-GRM3 signaling mediates anorexigenic effects via PI3K-AKT signaling. Of note, we verify the connections between deficiencies in the sleeping state, impaired Raptin release, and obesity in patients with sleep deficiency. Moreover, humans carrying an RCN2 nonsense variant present with night eating syndrome and obesity. These data define a unique hormone that suppresses food intake and prevents obesity.
研究领域:
神经科学
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内分泌学
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代谢研究
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睡眠医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURE GENETICS
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2025
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IF 29
Liu Qian,Liu Hui,Sun Lili,Wang Dekai,Sun Xueyuan,Wu Kun,Ye Yafeng,Wang Yun,Wang Shuoxun,Zhong Nan,Wu Xiaokang,Li Yu,Deng Min,Wang Meiyue,Wu Chenchen,Liu Xueying,Zhang Yijing,Xiao Jun,Wu Yuejin,Fu Xiangdong
Continuous and excessive use of inorganic fertilizers underlies current global crop production; therefore, reducing fertilizer use while increasing crop productivity is critical for ensuring agricultural sustainability and food security. Here we show that the natural variant of RCN2 , a rice TERMINAL FLOWER 1/CENTRORADIALIS homolog, enhances photosynthesis, nitrogen assimilation and grain yield by restricting chromatin loop extrusion. RCN2 competitively inhibits the interaction between growth-repressing DELLA proteins and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factors, breaking the green revolution trade-off between plant growth and metabolism of carbon and nitrogen. We demonstrate that targeting CCCTC-containing insulator elements at the RCN2 locus confers not only decoupling tillering and panicle branching without affecting beneficial semi-dwarfism, but also improves source-to-sink carbon allocation and nitrogen-use efficiency, consequently increasing harvest index and rice yield at low nitrogen fertilization levels. Precise modulation of loop extrusion thus enables new breeding strategies to reduce nitrogen fertilizer use in high-yield cereal crops.
研究领域:
植物分子生物学
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作物遗传育种
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表观遗传学
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植物生理学
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农业可持续发展
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氮代谢
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基因组结构与功能
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）