BIOLOGY OF REPRODUCTION
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2025
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IF 3
Liao Shiying,Cheng Jinhua,Zhao Weimin,Dai Chaohui,Fu Yanfeng,Li Bixia,Deng Yanfei,Li Hui
Kynurenine (KYN) is a primary tryptophan derivative found in the human body and fermented foods. Previous studies have shown that KYN is an Aryl hydrocarbon receptor (AHR) agonist and is important in regulating various physiological activities, including female reproduction. Progesterone is a vital steroid hormone that facilitates embryo implantation and maintains pregnancy. However, whether KYN affects its biosynthesis remains unclear. To gain understanding, in vitro luteinized porcine granulosa luteal (pGL) cells were treated with KYN. The results showed that KYN disrupted progesterone biosynthesis by decreasing the expression of STAR and HSD3B in pGL cells. In addition, the expression of three transcription factors of STAR and HSD3B (GATA4, GATA6, and CEBPB) decreased after KYN treatment. Furthermore, the AHR blockade results showed comparable to those of KYN treatment, and subsequent knockdown experiments confirmed these results. These findings suggest that KYN inhibits progesterone biosynthesis in pGL cells by downregulating GATA4, GATA6, and CEBPB expression through AHR. Thus, our results showed for the first time, a previously unknown connection between KYN and progesterone biosynthesis.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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高影响因子
JOR Spine
·
2024
·Vol. 7
·期 4
·e70004
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IF 3.4
Daqian Zhou,Tao Liu,Yongliang Mei,Jiale Lv,Kang Cheng,Weiye Cai,Silong Gao,Daru Guo,Xianping Xie,Zongchao Liu
Background Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
研究领域:
分子生物学
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生物信息学
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骨科医学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Wei Li,Xiao Wang,Xiaoli Liu,Luoyang Wang,Jie Liang,Yu Cui,Yi Liu,Mengting Zhou,Zijie Yang,Meiying Song,Yanyan Yang,Li Zhang,Bei Zhang
Persistent inflammation impedes peripheral nerve regeneration, in which infiltrating macrophages play pivotal roles by regulating the M1/M2 phenotypic balance. M2 macrophages facilitate repair, yet factors driving M1-to-M2 transition remain unclear. Lactate, a key metabolic byproduct in injured tissue, dynamically regulates microenvironmental signaling. Here, we observed a correlation between M2 macrophage accumulation and lactate elevation within 5 days post-sciatic nerve injury. In vitro, both Schwann cells and macrophages were identified as important lactate producers. In vivo, low-dose lactate (10–20 mM) enhanced M2 polarization and accelerated regeneration, whereas high-dose lactate (50 mM) showed no benefit. Transcriptomic analysis revealed that 10 mM lactate upregulated M2 markers (arginase 1 (Arg1), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β)) and oxidative phosphorylation (OXPHOS)-related genes in M1 macrophages. Seahorse analysis and adenosine triphosphate (ATP) quantification confirmed lactate-driven OXPHOS activation. Conversely, 50 mM lactate induced excessive reactive oxygen species (ROS) and reduced mitochondrial membrane potential which may explain its lack of regenerative efficacy. Furthermore, CCAAT/enhancer-binding protein beta (Cebpb), a transcription factor can promote Arg1 and VEGF expression in M1 cells under 20 mM lactate. Our findings demonstrate that low-dose lactate promotes M1-to-M2 transition via OXPHOS metabolic reprogramming and Cebpb upregulation, whereas excessive lactate disrupts mitochondrial function. This highlights lactate concentration-dependent modulation of macrophage polarization, a finding that provides insights into metabolic regulation of inflammatory responses during nerve repair. The current data, which focus on macrophage polarization outcomes, support further investigation into whether targeting metabolic rewiring could optimize regenerative microenvironments for functional nerve regeneration.
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Cell Reports
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2026
·Vol. 45
·期 8
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IF 7.7
Jing Wu,Zihan Chen,Shengxiang Yin,Yunqiang Chen,Tianxin Zhang,Yaoyao Gao,Yanfei Wei,Yuhua Liu,Fangji Yang,Ling Sang,Xuesong Liu,Yongxiang Liu,Wenting Zhu,Yuheng Shi,Nan Qi
Dysregulation of innate immunity during respiratory RNA virus infections drives systemic hyperinflammation and lung injury. Here, we show that importin β4 (IPO4) has a role in inhibiting antiviral innate immunity. Transcriptomics analysis illustrated a downregulation of IPO4 in alveolar macrophages, lung ciliated epithelium, and peripheral blood mononuclear cells from severely ill patients with COVID-19 or influenza. We further identified CCAAT/enhancer-binding protein beta (CEBPB) as the transcription factor for IPO4 reduction during RNA viral infections. Loss-of-function validation demonstrated that IPO4 dampens the innate antiviral and inflammatory responses in vitro and in vivo . Mechanistically, IPO4 sequesters fatty acid synthase (FASN) to block palmitic acid production, thereby inhibiting mitochondrial antiviral signaling protein (MAVS) activation and the downstream innate immune signaling. Moreover, Adeno-associated virus (AAV)-mediated pulmonary restoration of IPO4 significantly alleviated viral pneumonia in mice. These results indicate that the CEBPB-IPO4-FASN-MAVS axis preserves innate immune homeostasis to avoid inflammatory pathology, highlighting IPO4 as a potential therapeutic target for severe viral pneumonia.
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