Molecular immunology最新文献

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S1PR2-miR-212 feedback loop regulates allergic reactions S1PR2-miR-212反馈回路调节过敏反应。
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-06 DOI: 10.1016/j.molimm.2025.10.001
Jaewhoon Jeoung, Hyein Jo, Wonho Kim, Dooil Jeoung
{"title":"S1PR2-miR-212 feedback loop regulates allergic reactions","authors":"Jaewhoon Jeoung,&nbsp;Hyein Jo,&nbsp;Wonho Kim,&nbsp;Dooil Jeoung","doi":"10.1016/j.molimm.2025.10.001","DOIUrl":"10.1016/j.molimm.2025.10.001","url":null,"abstract":"<div><div>We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions <em>in vitro</em> and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions <em>in vitro</em>. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 166-177"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MAP30 inhibits proliferation and metastasis of bladder cancer by increasing EGR1 expression and promoting the transcriptional activation of DUSP1 MAP30通过增加EGR1的表达和促进DUSP1的转录激活来抑制膀胱癌的增殖和转移
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-06 DOI: 10.1016/j.molimm.2025.08.024
Kaiyue Wang , Qiao Gu , Chunyan Xue , Junyu Shi , Kun Wang , Xiaozhou He
{"title":"MAP30 inhibits proliferation and metastasis of bladder cancer by increasing EGR1 expression and promoting the transcriptional activation of DUSP1","authors":"Kaiyue Wang ,&nbsp;Qiao Gu ,&nbsp;Chunyan Xue ,&nbsp;Junyu Shi ,&nbsp;Kun Wang ,&nbsp;Xiaozhou He","doi":"10.1016/j.molimm.2025.08.024","DOIUrl":"10.1016/j.molimm.2025.08.024","url":null,"abstract":"<div><div>The confirmed tumor-inhibitory effects of the 30 kDa Momordica anti-human immunodeficiency virus protein (MAP30) have yet to be complemented by an exploration into its mechanism of action on tumor development and metastasis. For this purpose, we delved into the intrinsic mechanism of MAP30 in bladder cancer (BC). Here, we demonstrated that MAP30 markedly suppressed the proliferation, migration, invasion, and angiogenic capabilities of human BC cells <em>in vitro</em>, and the tumor metastatic potential <em>in vivo</em>. Furthermore, our findings showed that MAP30 suppressed the functional activities of BC cells by upregulating the expression levels of early growth response 1 (EGR1). Additionally, our investigation confirmed that EGR1 and dual specificity phosphatase 1 (DUSP1) were down-expressed in BC and had been identified as closely linked to the advancement of BC. DUSP1 was transcriptionally induced by EGR1, and the expression of EGR1 was found to be positively linked with DUSP1 in human BC tissues. The knockdown of EGR1 was found to boost cell invasion, migration, proliferation, and angiogenesis via the MAPK signaling pathway, however, the overexpression of DUSP1 inhibited EGR1 knockdown-induced promotion of these functional activities in BC cells. Furthermore, MAP30 inhibited the invasion, migration, proliferation, and angiogenesis of BC cells by regulating the EGR1-DUSP1 axis. Our study yielded an exhaustive insight into the suppressive actions of MAP30 on BC progression.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 48-60"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers 单色绿光介导的褪黑素促进肉鸡盲肠屏障功能
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-19 DOI: 10.1016/j.molimm.2025.09.004
Tao Quan, Ran Li, Yaoxing Chen, Ting Gao
{"title":"Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers","authors":"Tao Quan,&nbsp;Ran Li,&nbsp;Yaoxing Chen,&nbsp;Ting Gao","doi":"10.1016/j.molimm.2025.09.004","DOIUrl":"10.1016/j.molimm.2025.09.004","url":null,"abstract":"<div><div>Light plays a crucial role as an environmental factor, greatly affecting chick behavior, production performance and health. Melatonin, an essential marker of photoelectric signaling, plays a role in regulating various physiological functions in broilers, such as gut health. However, whether monochromatic light can mediate melatonin secretion to regulate intestinal function and its regulatory mechanism are not known. In the present study, we showed that monochromatic green light significantly enhanced the mucosal barrier function of the broiler cecum, including the up-regulation of goblet cells and their secreted MUC2 content, tight junction protein expression and enterocyte proliferative viability. However, when the pineal gland was removed, accompanied by a decrease in melatonin content, the green light advantage disappeared and the intestinal mucosal barrier function was severely impaired. Mechanistically, we found that monochromatic green light promotes melatonin secretion, which enters the intestine to bind Mel1a receptors located on macrophage membranes in cecum, inhibits its downstream TLR4/ERK/JNK/NF-κB signaling pathway, promotes M2-type macrophage polarization, reduces intestinal inflammation levels while up-regulating intestinal antioxidant levels, and ultimately strengthens the cecum mucosal barrier function. Our findings provide new theoretical support for the future use of melatonin during intestinal development, as well as theoretical guidance for the proper application of artificial lighting in the modern chicken industry to improve chicken's intestinal health.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 109-120"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis 溃疡性结肠炎体内微环境中氧化应激和转录程序异质性的表征
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-09 DOI: 10.1016/j.molimm.2025.08.017
Yongwei Zhuang , Ran Ye , Jingyu Chen , Gefei Chen , Luyi Chen , Yabi Zhu , Shufang Ye , Yangyang Liu
{"title":"Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis","authors":"Yongwei Zhuang ,&nbsp;Ran Ye ,&nbsp;Jingyu Chen ,&nbsp;Gefei Chen ,&nbsp;Luyi Chen ,&nbsp;Yabi Zhu ,&nbsp;Shufang Ye ,&nbsp;Yangyang Liu","doi":"10.1016/j.molimm.2025.08.017","DOIUrl":"10.1016/j.molimm.2025.08.017","url":null,"abstract":"<div><h3>Objective</h3><div>Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.</div></div><div><h3>Methods</h3><div>Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.</div></div><div><h3>Results</h3><div>Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R<sup>+</sup> myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4<sup>+</sup> naïve T cells, CD8<sup>+</sup> cytotoxic T cells, CD4<sup>+</sup> exhausted T cells, CD8<sup>+</sup> memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4<sup>+</sup> exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8<sup>+</sup> cytotoxic T cells.</div></div><div><h3>Conclusion</h3><div>Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 80-95"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Profiling of SFTS virus and host protein interactions by affinity purification-mass spectrometry SFTS病毒与宿主蛋白相互作用的亲和纯化-质谱分析
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-09-09 DOI: 10.1016/j.molimm.2025.09.001
Wen Hou , Jiansen Lu , Hao Pan , Tao Wang , Hongyun Liu , Ruibing Chen
{"title":"Profiling of SFTS virus and host protein interactions by affinity purification-mass spectrometry","authors":"Wen Hou ,&nbsp;Jiansen Lu ,&nbsp;Hao Pan ,&nbsp;Tao Wang ,&nbsp;Hongyun Liu ,&nbsp;Ruibing Chen","doi":"10.1016/j.molimm.2025.09.001","DOIUrl":"10.1016/j.molimm.2025.09.001","url":null,"abstract":"<div><div>Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the novel phlebovirus SFTSV (SFTS bunyavirus), was first identified in 2009 across several Chinese provinces, with a case fatality rate reaching 30 %. Given its compact genome, SFTSV critically depends on host cellular machinery for replication and pathogenesis. In this study, we employed a systematic strategy combining co-immunoprecipitation of viral-host complexes with formaldehyde crosslinking and affinity purification-mass spectrometry (AP-MS) to comprehensively map SFTSV-host interactions. We systematically analyzed protein complexes associated with all five viral structural/non-structural proteins (NP, NSs, Gc, Gn, and L), identifying 432 host proteins as potential viral interactors. Subsequent bioinformatic analysis included Gene Ontology categorization and functional domain/pathway enrichment analysis via KEGG, with interaction networks visualized through Cytoscape. Importantly, we experimentally validated key interactions between NSs and host proteins VDAC1, Vimentin, and HSP90AB1, demonstrating robust consistency with our mass spectrometry findings.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 96-108"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Regulation of macrophage pyroptosis by SIRT1 during Pseudomonas aeruginosa-induced pneumonia” (Mol. Immunol. 185 (2025) 7110) “铜绿假单胞菌诱导肺炎期间SIRT1对巨噬细胞热亡的调节”的更正(Mol. Immunol. 185(2025) 7110)。
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-16 DOI: 10.1016/j.molimm.2025.09.007
Haibo Ding , Xinzhu Xiao , Yuping Zhan , Yanqing Lin , Changsheng Xu , Yiming Zeng
{"title":"Corrigendum to “Regulation of macrophage pyroptosis by SIRT1 during Pseudomonas aeruginosa-induced pneumonia” (Mol. Immunol. 185 (2025) 7110)","authors":"Haibo Ding ,&nbsp;Xinzhu Xiao ,&nbsp;Yuping Zhan ,&nbsp;Yanqing Lin ,&nbsp;Changsheng Xu ,&nbsp;Yiming Zeng","doi":"10.1016/j.molimm.2025.09.007","DOIUrl":"10.1016/j.molimm.2025.09.007","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Page 254"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Small-molecule perturbation profiling reveals a mechanistic link between STING signaling and lipid metabolism in macrophages and dendritic cells 小分子摄动分析揭示了巨噬细胞和树突状细胞中STING信号与脂质代谢之间的机制联系。
IF 3 3区 医学
Molecular immunology Pub Date : 2025-11-01 Epub Date: 2025-10-17 DOI: 10.1016/j.molimm.2025.09.010
Lilah Gmyrek, Jianan Zhang, Maria Andrade, Kathryn R. Hillette, Xu Wu, Jin Mo Park
{"title":"Small-molecule perturbation profiling reveals a mechanistic link between STING signaling and lipid metabolism in macrophages and dendritic cells","authors":"Lilah Gmyrek,&nbsp;Jianan Zhang,&nbsp;Maria Andrade,&nbsp;Kathryn R. Hillette,&nbsp;Xu Wu,&nbsp;Jin Mo Park","doi":"10.1016/j.molimm.2025.09.010","DOIUrl":"10.1016/j.molimm.2025.09.010","url":null,"abstract":"<div><div>The DNA sensor cGAS and the signaling adaptor STING play a key role in the innate immune response to microbial and endogenous DNA in the cytoplasm. The cGAS-STING signaling pathway has evolved to promote immune defense and organismal fitness, yet its dysregulation can lead to chronic inflammation, autoimmunity, and neurodegeneration. Upon sensing double-stranded DNA, cGAS produces a cyclic dinucleotide second messenger that binds to STING in the endoplasmic reticulum. Ligand-bound STING translocates to the Golgi and activates a signaling cascade that results in interferon (IFN) gene transcription. These molecular events are mechanistically linked to intracellular lipid membrane dynamics and protein lipidation. To explore whether STING signaling is controlled by the availability and metabolic flux of cellular lipids, we screened small-molecule compounds targeting lipid metabolic pathways for their influence on STING agonist-responsive IFN induction. These screens identified inhibitors of the fatty acid synthase FAS and lipases as potent suppressors of STING signaling. An inhibitor of the cholesterol-esterifying enzyme SOAT1 enhanced STING-dependent IFN induction in mouse cells while attenuating it in human cells. From an analysis of STING sequences, we detected a difference in their lipid binding motifs that likely accounted for the species-specific effects of SOAT1 inhibition. Our findings reveal a connection between STING signaling and lipid metabolism and opportunities for expanding the toolbox for treating clinical conditions that arise from aberrant STING activity.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 255-262"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bta-miR-25 alleviates lipopolysaccharide-induced endometritis in cows by targeting DUSP10 to inhibit MAPK signaling Bta-miR-25通过靶向DUSP10抑制MAPK信号传导来缓解脂多糖诱导的奶牛子宫内膜炎
IF 3 3区 医学
Molecular immunology Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1016/j.molimm.2025.07.015
Zhihao Zhang , Xiangnan Wang , Qiao ting Shi , Li gang Lu , Xiang zhou Yan , Xingshan Qi , Zi jing Zhang , Er yao Wang
{"title":"Bta-miR-25 alleviates lipopolysaccharide-induced endometritis in cows by targeting DUSP10 to inhibit MAPK signaling","authors":"Zhihao Zhang ,&nbsp;Xiangnan Wang ,&nbsp;Qiao ting Shi ,&nbsp;Li gang Lu ,&nbsp;Xiang zhou Yan ,&nbsp;Xingshan Qi ,&nbsp;Zi jing Zhang ,&nbsp;Er yao Wang","doi":"10.1016/j.molimm.2025.07.015","DOIUrl":"10.1016/j.molimm.2025.07.015","url":null,"abstract":"<div><div>Bovine endometritis is a common and serious disease that has caused huge economic losses and a decline in production performance in the dairy cattle industry. This study aimed to investigate the regulatory role of bta-miR-25 in Lipopolysaccharide (LPS)-induced BEND and its impact on endometritis. In this study, an <em>in vitro</em> endometritis model was constructed using LPS. The expression levels of proinflammatory cytokines <em>IL-6, IL-8, IL-1β, and TNF-α</em> were significantly increased in the model, while the expression of bta-miR-25 was upregulated, and its target gene DUSP10 was downregulated. We further validated <em>DUSP10</em> as a target gene of bta-miR-25 through a dual-luciferase reporter gene assay. Knockdown of bta-miR-25 can increase the decreased expression of DUSP10 levels and inhibited the increase in inflammatory factors induced by LPS. Subsequently, overexpression <em>DUSP10</em> also inhibited the LPS-induced increase in inflammatory factors. In summary, bta-miR-25 can inhibit LPS-induced endometritis by over the expression of <em>DUSP10</em>. bta-miR-25 and <em>DUSP10</em> may serve as biomarkers and potential therapeutic targets for endometritis in dairy cows.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 39-47"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gelatin enhances bacteria-phagocytosis via a ROS-mitochondria-STING axis in differentiated human macrophage-like U937 cells 明胶通过ros -线粒体- sting轴增强分化的人巨噬细胞样U937细胞的细菌吞噬作用
IF 3 3区 医学
Molecular immunology Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1016/j.molimm.2025.08.011
Xiaoli Sun , Meiling Li , Yuhang Ma , Kaihui Chen , Shunuo Jiang , Toshihiko Hayashi , Kikuji Itoh , Kazunori Mizuno , Shunji Hattori , Hitomi Fujisaki , Weiwei Liu , Takashi Ikejima
{"title":"Gelatin enhances bacteria-phagocytosis via a ROS-mitochondria-STING axis in differentiated human macrophage-like U937 cells","authors":"Xiaoli Sun ,&nbsp;Meiling Li ,&nbsp;Yuhang Ma ,&nbsp;Kaihui Chen ,&nbsp;Shunuo Jiang ,&nbsp;Toshihiko Hayashi ,&nbsp;Kikuji Itoh ,&nbsp;Kazunori Mizuno ,&nbsp;Shunji Hattori ,&nbsp;Hitomi Fujisaki ,&nbsp;Weiwei Liu ,&nbsp;Takashi Ikejima","doi":"10.1016/j.molimm.2025.08.011","DOIUrl":"10.1016/j.molimm.2025.08.011","url":null,"abstract":"<div><div>The recruitment of macrophages to a pathological site is accompanied by the change in surrounding extracellular matrix. The pathological foci in a highly inflammatory status contain certain amounts of gelatin, the denatured form of collagen. We previously revealed that precoating the cell dishes with gelatin, but not type I collagen, enhances bacteria-phagocytosis capacity of phorbol 12-myristate 13-acetate (PMA)-treated macrophage-like human histiocytic lymphoma U937 cells. The present study further reveals that gelatin-precoating increases the amount of reactive oxygen species (ROS) in PMA-treated U937 cells, which contributes to the enhanced phagocytosis of bacteria, including both Gram-negative <em>Escherichia coli</em> and Gram-positive <em>Staphylococcus aureus</em>. ROS in cells on gelatin-precoated culture plates cause impairments on mitochondria, as shown by the reduced mitochondrial membrane potential and ATP levels, as well as the increase in oxidative lesions in mitochondrial DNA. These mitochondrial damages lead to the activation of stimulator of interferon genes (STING) pathway, which enhances the bacteria-phagocytosis in PMA-treated U937 cells. Simultaneously, mitophagy-related proteins, such as PINK1, parkin and LC3 II, all increase following the elevation of ROS levels. Of note, mitophagy restricts the mitochondrial disorders, forming a feedback negative regulation for the effects of ROS, and works against bacteria-phagocytosis. This study reveals a core function of ROS-mitochondria-STING axis during gelatin-enhanced bacteria-phagocytosis in PMA-stimulated macrophage-like U937 cells, and provides possibility for clinically applying gelatin as a protectant for bacterial infection in some lesions.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 48-62"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The circERBB3/chi-miR-181b-5p/TNFSF11 axis regulates proliferation, migration, and apoptosis in cashmere goat embryonic fibroblasts circERBB3/chi-miR-181b-5p/TNFSF11轴调控绒山羊胚胎成纤维细胞的增殖、迁移和凋亡
IF 3 3区 医学
Molecular immunology Pub Date : 2025-10-01 Epub Date: 2025-08-26 DOI: 10.1016/j.molimm.2025.08.001
Youjun Rong , Jianfeng Pan , Shuran Niu , Xiaofang Ao , Yihan Wang , Fangzheng Shang , Qi Lv , Zhiying Wang , Ruijun Wang , Rui Su , Yanhong Zhao , Yu Wang , Yanjun Zhang
{"title":"The circERBB3/chi-miR-181b-5p/TNFSF11 axis regulates proliferation, migration, and apoptosis in cashmere goat embryonic fibroblasts","authors":"Youjun Rong ,&nbsp;Jianfeng Pan ,&nbsp;Shuran Niu ,&nbsp;Xiaofang Ao ,&nbsp;Yihan Wang ,&nbsp;Fangzheng Shang ,&nbsp;Qi Lv ,&nbsp;Zhiying Wang ,&nbsp;Ruijun Wang ,&nbsp;Rui Su ,&nbsp;Yanhong Zhao ,&nbsp;Yu Wang ,&nbsp;Yanjun Zhang","doi":"10.1016/j.molimm.2025.08.001","DOIUrl":"10.1016/j.molimm.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Inner Mongolia cashmere goat is an excellent local variety of both cashmere and meat. Its cashmere is delicate and soft and has high economic value. The morphogenesis and development of hair follicles directly affect the wool yield and quality of cashmere goats. Circular RNAs are endogenous, non-coding RNAs found in eukaryotic genomes that are involved in a variety of physiological and pathological processes. However, the potential function of circRNA in the development of embryonic skin hair follicles in cashmere goats remains unknown.</div></div><div><h3>Results</h3><div>In this study, we identified a novel circular RNA, circERBB3, isolated fibroblasts from cashmere goat embryonic skin tissue, and investigated its role in fibroblast proliferation, apoptosis, and migration. The interaction between circERBB3, chi-miR-181b-5p, and <em>TNFSF11</em> was detected by bioinformatics, real-time quantitative PCR, and the dual luciferase reporter gene system. Mechanistically, we demonstrated the functional significance of circERBB3 by interfering with circERBB3 in fibroblasts. At the molecular and cellular levels, co-transfection tests confirmed that circERBB3 negatively regulated fibroblast proliferation, apoptosis, and migration in a chi-miR-181b-5p-dependent manner. Chi-miR-181b-5p can regulate the proliferation, apoptosis, and migration of fibroblasts by targeting <em>TNFSF11</em>.</div></div><div><h3>Conclusions</h3><div>As a competitive endogenous RNA, circERBB3 binds to chi-miR-181b-5p and alleviates the inhibition of its target gene, <em>TNFSF11</em>, to regulate the proliferation, apoptosis, and migration of embryonic fibroblasts in cashmere goats. A new regulatory pathway regulating the development of hair follicles was revealed.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 174-185"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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