Molecular immunology最新文献

{"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":"2025-09-06","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}

{"title":"Study on the adjuvant activity and mechanism of action of a novel Monophosphoryl Lipid A","authors":"Lichun Zhao,&nbsp;Peixin Shi,&nbsp;Yujiao Zhang,&nbsp;Mingxuan Zhang,&nbsp;Na Han,&nbsp;Zhihui Liu,&nbsp;Sikai Li,&nbsp;Jun Yin,&nbsp;Jianxiu Zhai","doi":"10.1016/j.molimm.2025.08.019","DOIUrl":"10.1016/j.molimm.2025.08.019","url":null,"abstract":"<div><div>In order to develop a novel vaccine adjuvant that is highly efficient, cost-effective, and suitable for widespread application, this study employed synthetic biology techniques to produce a new type of <em>Escherichia coli</em> monophosphate lipid A (N-MPL). Specifically, the phosphate group attached to the C-1 position was removed, and a hydroxyl group was introduced into the 3′-secondary fatty acid chain of the original lipid A structure. This modification aimed to reduce toxicity while enhancing water solubility. Two formulations of N-MPL were prepared and their immunological and adjuvant activities were evaluated. Results demonstrated that both formulations could promote the proliferation of immune cells and the maturation of bone marrow-derived dendritic cells (BMDCs). In an adjuvant immunization experiment using H1N1 vaccine in ICR mice, N-MPL exhibited superior adjuvant effects compared to aluminum adjuvants and commercially available Monophosphoryl Lipid A (Synthetic) (PHAD™). Through comprehensive analysis of splenic lymphocytes, antibodies, cytokines, and immune factors in immunized mice, it was discovered for the first time that different formulations of N-MPL adjuvants could regulate cellular and humoral immunity, albeit with distinct foci of induced immune responses. The oil-in-water formulation of N-MPL primarily induced cellular immune responses in mice, whereas the aqueous solution formulation predominantly elicited humoral immune responses. Mechanistic studies revealed that N-MPL regulates the Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway. Overall, the novel N-MPL adjuvant exhibits high efficiency and low cost, demonstrating significant potential for vaccine adjuvant development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 28-47"},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933540","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}

{"title":"SMAD7-mediated ferroptosis in macrophages drives osteoporosis progression: A multi-omics study","authors":"Qianning Li ,&nbsp;Yucheng Tu ,&nbsp;Hengyi Diao ,&nbsp;Linli Zheng ,&nbsp;Weishen Chen","doi":"10.1016/j.molimm.2025.08.021","DOIUrl":"10.1016/j.molimm.2025.08.021","url":null,"abstract":"<div><div>Osteoporosis (OP) is characterized by imbalanced bone homeostasis, which is difficult to precisely regulate with current therapeutic strategies. Macrophages play a significant role in bone remodeling due to their complex interactions with osteoclasts and osteoblasts, suggesting that targeting macrophage-related pathways could offer novel therapeutic opportunities. To explore this, we combined bulk RNA-seq and scRNA-seq data to identify macrophage-related genes. Using bioinformatic tools, including CIBERSORT, WGCNA, and machine learning algorithms, we identified 1705 macrophage marker genes and 839 macrophage module genes. Enrichment analysis revealed that the intersection genes were significantly enriched in the ferroptosis signaling pathway, highlighting its critical role in macrophages. Further validation through protein-protein interaction networks and cellular communication analysis confirmed the importance of ferroptosis in macrophage. Using artificial neural network, we identified 4 macrophage hub genes, with SMAD7 showing the greatest weight. Experimental validation using RAW264.7 cells, immunohistochemistry, and micro-CT analysis further demonstrated the association of ferroptosis-related indicators (Fe^2 + and lipid peroxidation) with bone damage in osteoporosis patients. And we found SMAD7 showing the strongest correlation with trabecular microstructural deterioration. Notably, our findings also confirmed that the SMAD7 inhibitor mongersen effectively attenuated macrophage ferroptosis, suggesting its potential to improve bone microstructural integrity. Our study demonstrates that SMAD7-mediated macrophage ferroptosis is a critical mechanism in osteoporosis pathogenesis, highlighting SMAD7 as a promising therapeutic target.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 11-27"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921145","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}

{"title":"CCL5: An emerging key target and progress in the targeted therapy of hepatocellular carcinoma","authors":"Xiaoli Liu ,&nbsp;Jie Liang ,&nbsp;Lizhen Zhao ,&nbsp;Wei Li ,&nbsp;Luoyang Wang ,&nbsp;Xiao Wang ,&nbsp;Yi Liu ,&nbsp;Mengting Zhou ,&nbsp;Xinqiang Li ,&nbsp;Zhuoyu Jia ,&nbsp;Meiying Song ,&nbsp;Li Zhang ,&nbsp;Yanyan Yang ,&nbsp;Jinzhen Cai ,&nbsp;Bei Zhang","doi":"10.1016/j.molimm.2025.08.023","DOIUrl":"10.1016/j.molimm.2025.08.023","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy, presenting significant challenges in clinical diagnosis and treatment. The chemokine C-C motif ligand 5 (CCL5) plays a pivotal role in HCC pathogenesis. While traditionally viewed primarily as a mediator of immune cell chemotaxis and migration, recent evidence demonstrates that CCL5 directly influences tumor cells, regulating malignant behaviors such as proliferation and invasion. Furthermore, CCL5 recruits diverse immune cells, including immunosuppressive populations, to the tumor microenvironment (TME), remodeling the TME and exerting context-dependent effects that can either promote immune evasion or enhance anti-tumor immunity. This article reviews advances in understanding the mechanisms of CCL5 in HCC and discusses the translational potential of targeting CCL5 for HCC therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912995","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}

{"title":"JAK/STAT pathway in myocardial infarction: Crossroads of immune signaling and cardiac remodeling","authors":"Qiufen Yang ,&nbsp;Huiliang Ji ,&nbsp;Amir Modarresi Chahardehi","doi":"10.1016/j.molimm.2025.08.018","DOIUrl":"10.1016/j.molimm.2025.08.018","url":null,"abstract":"<div><div>Myocardial infarction (MI) initiates a robust immune-inflammatory response in which dysregulated cytokine signaling exacerbates tissue damage and adverse cardiac remodeling. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway serves as a key mediator of cytokine signaling and immune cell activation, playing a dual role in post-MI outcomes. On one hand, JAK/STAT activation supports cardioprotective mechanisms such as angiogenesis and anti-apoptotic signaling; on the other hand, its excessive or prolonged activation contributes to maladaptive inflammation, fibrosis, and heart failure. This review examines how pro-inflammatory cytokines (e.g., IL-6, TNF-α) and immune cells (e.g., macrophages, neutrophils) activate the JAK/STAT pathway in ischemic myocardium. We discuss the pathway’s crosstalk with inflammatory signaling networks, including NF-κB, MAPK, and PI3K/Akt, and evaluate the potential of repurposing JAK inhibitors (e.g., ruxolitinib) to modulate immune responses after MI, drawing insights from clinical trials in autoimmune diseases. Unresolved challenges such as cell-specific effects of JAK/STAT modulation and the need for biomarker-driven therapies are also highlighted. By synthesizing current preclinical and clinical evidence, this review proposes a framework for immune-targeted strategies aimed to improving cardiac outcomes following MI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 206-217"},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908304","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}

{"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":"2025-08-26","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}

{"title":"An indirect ELISA for the detection of anti-NY-ESO-1 antibodies in cancer patients and for monitoring cancer therapy","authors":"Ji Luo ,&nbsp;Sanja Milkovska-Stamenova ,&nbsp;Julia Karbach ,&nbsp;Elke Jäger ,&nbsp;Ralf Hoffmann ,&nbsp;Jörg Gabert","doi":"10.1016/j.molimm.2025.08.009","DOIUrl":"10.1016/j.molimm.2025.08.009","url":null,"abstract":"<div><div>Early diagnosis of cancer offers the best chance for effective treatment. Serological tests for the detection of cancer testis antigens (CTA) could aid in cancer diagnosis, prognosis, and treatment evaluation. Since NY-ESO-1 induces a strong immune response in several cancer types, it is considered an attractive CTA for antibody assay development. The full-length NY-ESO-1 protein was recombinantly produced in <em>Escherichia coli</em>, purified, and used to develop an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of NY-ESO-1 specific antibodies. This ELISA was optimized and validated using serum samples collected from 78 confirmed cancer patients and control sera from healthy donors (n = 20) and rheumatoid arthritis patients (n = 43). The optimized NY-ESO-1 ELISA provided a sensitivity of 96.2 % in cancer patients and a specificity of 100 % for non-cancer donors. A follow-up study of patients undergoing cancer treatment indicated that the antibody levels were responsive to therapy, becoming very low or negative after successful treatment and rising again before tumor metastasis recurrence was confirmed. Comparative peptide ELISA using overlapping peptides of the full NY-ESO-1 sequence did not improve the detection rate, but did reveal common epitopes. The NY-ESO-1 protein-based ELISA could be used to detect potential cancer patients and is useful for monitoring cancer therapy and tumor recurrence after treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 186-192"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894978","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}

{"title":"Curcumin modulates tracheal epithelial cell autophagy in asthma by inhibiting the NF-κB pathway via SCGB3A2","authors":"Tao Wang ,&nbsp;Wenting Huang ,&nbsp;Liang Long ,&nbsp;Peng Fu ,&nbsp;Qiongping Wang ,&nbsp;Fa Long ,&nbsp;Shengming Liu","doi":"10.1016/j.molimm.2025.08.012","DOIUrl":"10.1016/j.molimm.2025.08.012","url":null,"abstract":"<div><h3>Background and objective</h3><div>Asthma, a chronic inflammatory airway disease, presents a significant global health burden. This study aimed to elucidate the mechanism by which curcumin modulates tracheal epithelial cell autophagy in asthma, with a specific focus on its interplay with SCGB3A2 and the NF-κB pathway.</div></div><div><h3>Methods</h3><div>An <em>in vitro</em> asthma model was mimicked using 16HBE cells treated with TDI. Concurrently, a TDI-induced asthma model was built in Balb/c mice for <em>in vivo</em> investigations. Cells or mice were subjected to curcumin treatment, and SCGB3A2 was knockdown or overexpressed, to explore the function of SCGB3A2. TNF-α and TPCA-1 were also utilized to mediate activation of NF-κB <em>in vitro</em>. Western blot, qPCR, ELISA, immunofluorescence, and transmission electron microscopy were employed to assess SCGB3A2 expression, NF-κB pathway activation, autophagy, key inflammatory cytokines, and airway remodeling indicators.</div></div><div><h3>Results</h3><div>TDI stimulation reduced SCGB3A2 expression in 16HBE cells. SCGB3A2 overexpression mitigated TDI-induced inflammation and airway remodeling by inhibiting the NF-κB pathway and enhancing autophagy. Subsequent NF-κB activation partially abrogated these SCGB3A2-mediated protective effects on inflammation, airway remodeling, and autophagy. Curcumin treatment upregulated SCGB3A2, inhibited NF-κB activation, and promoted autophagy; these protective effects were substantially diminished upon SCGB3A2 knockdown. <em>In vivo</em>, curcumin administration ameliorated asthma features, evidenced by reduced airway inflammation, suppressed NF-κB, and enhanced autophagy in tracheal epithelial tissues.</div></div><div><h3>Conclusions</h3><div>This study reveals that curcumin protects against asthma by modulating the SCGB3A2-NF-κB-autophagy axis. These findings highlight this axis as a novel therapeutic target for asthma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 193-205"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894979","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}

{"title":"The protective role of Astragaloside IV in adriamycin-induced renal injury: A focus on macrophage polarization and PPARγ activation","authors":"Aiping Li ,&nbsp;Mengjiao Wang ,&nbsp;Min Guo ,&nbsp;Yuetao Liu ,&nbsp;Ke Li ,&nbsp;Lichao Zhang ,&nbsp;Xuemei Qin ,&nbsp;Guangzhen Liu","doi":"10.1016/j.molimm.2025.08.015","DOIUrl":"10.1016/j.molimm.2025.08.015","url":null,"abstract":"<div><div>Astragali Radix (AR), a homologous of medicine and food, has been extensively recorded to possess a nephroprotective impact on individuals suffering from chronic kidney disease (CKD). Astragaloside IV (ASIV) is one of the prominent bioactive constituents derived from AR. This study aimed to investigate how ASIV promotes M2 polarization of macrophages and whether this contributes to the protection of podocytes from injury, using a combination of lipidomics and molecular biology techniques.The effect of ASIV on adriamycin (ADR)-induced renal injury in rats was evaluated in vivo, with a particular emphasis on elucidating the potential involvement of macrophages. The M1 polarization model of RAW264.7 cells induced by ADR was established in <em>vitro</em>. The impact of ASIV on ADR-induced macrophage polarization was comprehensively assessed by measuring the expression levels of M1 and M2 macrophage marker proteins, along with their associated mRNA profiles. Flow cytometry was employed to analyze surface marker expression, while Western blot (WB) was used to quantify protein levels, and real-time quantitative PCR (qPCR) allowed for the measurement of gene expression. Notably, we found that the macrophage supernatant intervened by ASIV was found to have a protective effect against podocyte injury, which was evaluated through cell adhesion and apoptosis assays. Innovatively, we explored the mechanism by which ASIV affects macrophage polarization from the perspective of lipid metabolism, using lipidomics methods. During this process, the role of peroxisome proliferator-activated receptor gamma (PPARγ) in macrophage polarization caught our attention. This receptor is closely associated with lipid metabolites, as confirmed by molecular docking. ASIV has been shown to effectively ameliorate kidney injury, with macrophages playing a pivotal role in renal podocyte repair process. The protein and mRNA expressions of ARG-1, CD206 and IL-10, M2 macrophage markers, was increased by ASIV and M2 macrophages polarization was promoted by ASIV (P &lt; 0.05). In addition, it was observed that the supernatant of macrophages intervened by ASIV exerts a protective effect on podocyte injury, which was confirmed through podocyte adhesion assays and cell apoptosis experiments. This study suggests that ASIV enhances the M2 polarization of macrophages, and the supernatant from these polarized macrophages has a protective effect on podocytes. From the perspective of lipid metabolism, the underlying mechanism of this effect may involve the modulation of sphingolipids, arachidonic acid, glycerophospholipids, and other lipid metabolites, which activate the receptor PPARγ, thereby exerting protective effects on podocytes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 161-173"},"PeriodicalIF":3.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894976","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}

{"title":"Exosomal miR-214–3p reprograms BMSC fate: A novel intercellular mechanism linking vascular insufficiency to impaired bone regeneration in nontraumatic ONFH","authors":"Shifan Lin,&nbsp;Jian Xia,&nbsp;Jian Ding,&nbsp;Jie Wan","doi":"10.1016/j.molimm.2025.08.014","DOIUrl":"10.1016/j.molimm.2025.08.014","url":null,"abstract":"<div><h3>Background</h3><div>Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating bone disorder of unclear etiology, characterized by impaired bone regeneration and reduced vascularization. However, the influence of NONFH-derived exosomes on bone marrow stromal cell (BMSC) differentiation and angiogenesis remains poorly understood.</div></div><div><h3>Methods</h3><div>Exosomes were isolated from femoral head tissues of NONFH patients and fracture controls (femoral neck fractures). Their characteristics were confirmed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. BMSCs were treated with different exosomes (control exosomes, NONFH exosomes, or NONFH exosomes + miR-214–3p inhibitor), and osteogenic/adipogenic differentiation was assessed by alkaline phosphatase activity, calcium deposition, osteogenic/adipogenic marker expression, and Oil Red O staining. Human umbilical vein endothelial cells (HUVECs) were similarly treated, and angiogenesis was evaluated via tube formation assays. In vivo, exosomes were injected into rats, and femoral changes were analyzed by Western blot, hematoxylin-eosin (HE) staining, and immunohistochemistry.</div></div><div><h3>Results</h3><div>Exosomes from both groups exhibited typical morphology, size, and marker expression. NONFH exosomes suppressed BMSC osteogenesis, enhanced adipogenesis, and impaired HUVEC angiogenesis, with miR-214–3p as a critical mediator. Inhibiting miR-214–3p partially restored osteogenic and angiogenic capacities. In rats, NONFH exosomes reduced osteogenic protein expression, expanded marrow cavities, and disrupted trabecular bone structure, while miR-214–3p inhibition ameliorated these effects.</div></div><div><h3>Conclusion</h3><div>NONFH-derived exosomes contribute to disease progression by delivering miR-214–3p, which inhibits BMSC osteogenesis and HUVEC angiogenesis. Targeting this pathway may offer novel therapeutic strategies for NONFH.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 147-160"},"PeriodicalIF":3.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889643","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}