International Journal of Molecular Sciences最新文献

Brain-Bone Axis in Physiological and Pathological Conditions. 生理和病理条件下的脑-骨轴。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199822

Luca Massaccesi, Massimiliano Marco Corsi Romanelli, Emanuela Galliera

引用次数: 0

CAP-LAMP2b-Modified Stem Cells' Extracellular Vesicles Hybrid with CRISPR-Cas9 Targeting ADAMTS4 to Reverse IL-1β-Induced Aggrecan Loss in Chondrocytes. cap - lamp2b修饰的干细胞胞外囊泡与靶向ADAMTS4的CRISPR-Cas9杂交逆转il -1β诱导的软骨细胞聚集蛋白丢失

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199812

Kun-Chi Wu, Yu-Hsun Chang, Raymond Yuh-Shyan Chiang, Dah-Ching Ding

{"title":"CAP-LAMP2b-Modified Stem Cells' Extracellular Vesicles Hybrid with CRISPR-Cas9 Targeting ADAMTS4 to Reverse IL-1β-Induced Aggrecan Loss in Chondrocytes.","authors":"Kun-Chi Wu, Yu-Hsun Chang, Raymond Yuh-Shyan Chiang, Dah-Ching Ding","doi":"10.3390/ijms26199812","DOIUrl":"10.3390/ijms26199812","url":null,"abstract":"Extracellular vesicles (EVs) from mesenchymal stem cells hold therapeutic promise for inflammatory and degenerative diseases; however, limited delivery and targeting capabilities hinder their clinical use. In this study, we sought to enhance the anti-inflammatory and chondroprotective effects of EVs through CAP-LAMP2b (chondrocyte affinity peptide fused to an EV membrane protein) engineering and ADAMTS4 gene editing hybrid vesicle formation. Human umbilical cord MSCs (hUCMSCs) were characterized via morphology, immunophenotyping, and trilineage differentiation. EVs from control and CAP-LAMP2b-transfected hUCMSCs were fused with liposomes carrying CRISPR-Cas9 ADAMTS4 gRNA. DiI-labeled EV uptake was assessed via fluorescence imaging. CAP-LAMP2b was expressed in hUCMSCs and their EVs. EVs exhibited the expected size (~120 nm), morphology, and exosomal markers (CD9, CD63, CD81, HSP70). CAP-modified hybrid EVs significantly enhanced chondrocyte uptake compared to control EVs and liposomes. IL-1β increased ADAMTS4 expression, whereas CAP-LAMP2b-ADAMTS4 EVs, particularly clone SG3, reversed these effects by reducing ADAMTS4 and restoring aggrecan. Western blotting confirmed suppressed ADAMTS4 and elevated aggrecan protein. CAP-LAMP2b-ADAMTS4 EVs, therefore, showed superior uptake and therapeutic efficacy in inflamed chondrocytes, attenuating inflammatory gene expression and preserving matrix integrity. These results support engineered EVs as a promising cell-free approach for cartilage repair and osteoarthritis treatment.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reactivation of the PI3K/mTOR Signaling Pathway Confers Resistance to the FGFR4 Inhibitor FGF401. PI3K/mTOR信号通路的重新激活赋予对FGFR4抑制剂FGF401的抗性

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199818

Hung Huynh, Wai Har Ng

{"title":"Reactivation of the PI3K/mTOR Signaling Pathway Confers Resistance to the FGFR4 Inhibitor FGF401.","authors":"Hung Huynh, Wai Har Ng","doi":"10.3390/ijms26199818","DOIUrl":"10.3390/ijms26199818","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a deadly liver cancer characterized by dysregulated signaling and aberrant cell-cycle control. The FGFR4/FGF19 pathway is dysregulated in HCC and other cancers. Inhibitors targeting the FGF19/FGFR4 pathway, including the FGF19/FGFR4 inhibitor FGF401, have been investigated in HCC and other cancers; however, nearly all patients who initially respond eventually develop resistance shortly after starting therapy, highlighting the urgent need for new treatment strategies to overcome drug resistance. In the present study, we report that chronic treatment of the FGF19/FGFR4-expressing HCC25-0705A line with FGF401 led to acquired resistance. FGF401-resistant tumors exhibited upregulation of FGFRs and activation of the PI3K/AKT/mTOR/p70S6K pathway. Combination therapy with FGF401 and the mammalian target of rapamycin (mTOR) inhibitor everolimus (FGF401/everolimus) resulted in more complete tumor growth inhibition, delayed the onset of resistance, and prolonged overall survival (OS) in mice bearing orthotopic HCC tumors. The FGF401/everolimus combination effectively suppressed tumor cell proliferation; promoted apoptosis; reduced tumor hypoxia via blood vessel normalization; and downregulated key proteins involved in proliferation, survival, metastasis, and angiogenesis. These preclinical findings provide a strong rationale for clinical trials combining FGFR4 and mTOR inhibitors in HCC patients with FGF19/FGFR4/mTOR-dependent tumors.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinformatics Analysis of Tumor-Associated Macrophages in Hepatocellular Carcinoma and Establishment of a Survival Model Based on Transformer. 肝癌肿瘤相关巨噬细胞的生物信息学分析及基于Transformer的生存模型的建立。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199825

Zhuo Zeng, Shenghua Rao, Jiemeng Zhang

{"title":"Bioinformatics Analysis of Tumor-Associated Macrophages in Hepatocellular Carcinoma and Establishment of a Survival Model Based on Transformer.","authors":"Zhuo Zeng, Shenghua Rao, Jiemeng Zhang","doi":"10.3390/ijms26199825","DOIUrl":"10.3390/ijms26199825","url":null,"abstract":"Hepatocellular carcinoma (HCC) ranks among the most prevalent malignancies globally. Although treatment strategies have improved, the prognosis for patients with advanced HCC remains unfavorable. Tumor-associated macrophages (TAMs) play a dual role, exhibiting both anti-tumor and pro-tumor functions. In this study, we analyzed single-cell RNA sequencing data from 10 HCC tumor cores and 8 adjacent non-tumor liver tissues available in the dataset GSE149614. Using dimensionality reduction and clustering approaches, we identified six major cell types and nine distinct TAM subtypes. We employed Monocle2 for cell trajectory analysis, hdWGCNA for co-expression network analysis, and CellChat to investigate functional communication between TAMs and other components of the tumor microenvironment. Furthermore, we estimated TAM abundance in TCGA-LIHC samples using CIBERSORT and observed that the relative proportions of specific TAM subtypes were significantly correlated with patient survival. To identify TAM-related genes influencing patient outcomes, we developed a high-dimensional, gene-based transformer survival model. This model achieved superior concordance index (C-index) values across multiple datasets, including TCGA-LIHC, OEP000321, and GSE14520, outperforming other methods. Our results emphasize the heterogeneity of tumor-associated macrophages in hepatocellular carcinoma and highlight the practicality of our deep learning framework in survival analysis.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polyphenols and Fibre: Key Players with Antioxidant Activity in Two Extracts from Pomegranate (Punica granatum). 多酚和纤维：两种石榴提取物中具有抗氧化活性的主要成分。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199807

Jessica Maiuolo, Federico Liuzzi, Francesca Oppedisano, Anna Spagnoletta, Rosamaria Caminiti, Valeria Mazza, Saverio Nucera, Salvatore Ragusa, Luigi Tucci, Giuseppe Trunfio, Lucia Carmela Passacatini, Sara Ilari, Giancarlo Statti, Vincenzo Mollace, Carolina Muscoli

{"title":"Polyphenols and Fibre: Key Players with Antioxidant Activity in Two Extracts from Pomegranate (Punica granatum).","authors":"Jessica Maiuolo, Federico Liuzzi, Francesca Oppedisano, Anna Spagnoletta, Rosamaria Caminiti, Valeria Mazza, Saverio Nucera, Salvatore Ragusa, Luigi Tucci, Giuseppe Trunfio, Lucia Carmela Passacatini, Sara Ilari, Giancarlo Statti, Vincenzo Mollace, Carolina Muscoli","doi":"10.3390/ijms26199807","DOIUrl":"10.3390/ijms26199807","url":null,"abstract":"The pomegranate fruit offers numerous health benefits to humans due to its rich composition of various chemical components, including polyphenols, fibre, flavonoids, minerals, vitamins, organic acids, alkaloids, and amino acids, among others. The antioxidant properties of pomegranate are well known, and this study aims to compare these activities in two extracts obtained from the fruit (\"Whole Fruit Extract\", WFE and \"Internal Membranes Extract\", IME). Various experiments were conducted using both extracts: (1) quantification of polyphenols and flavonoids using the Folin-Ciocalteu colorimetric assay and the aluminium chloride assay, respectively; (2) the measurement of the antioxidant activity was carried out by Reducing Power, Chelating Activity of Ferrous Ions (Fe2+), Radical Absorbance Capacity of Oxygen, Free Radical Scavenging Activity DPPH, and antioxidant effect in vitro; (3) quantitative and quantitative evaluation of the fibre was performed. IME has demonstrated a significantly greater antioxidant effect than WFE, despite possessing a smaller amount of both polyphenols and flavonoids (polyphenols: 68 mg GAE/g for WFE; 47 mg GAE/g for IME; flavonoids: 51mg QE/g for WFE; 35 mg QE/g for IME). For this reason, we evaluated the fibre composition in both extracts. The higher amount of glucans, xylans, and pectin in IME suggested that these fibrous components may be responsible for the greater antioxidant effect detected compared to WFE.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transthyretin Amyloidosis-One of the Causes of Heart Failure in Patients with Severe Clinical Course of COVID-19. 转甲状腺糖蛋白淀粉样变性- COVID-19重症临床病程患者心力衰竭的原因之一

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199806

Zarina Gioeva, Liudmila Mikhaleva, Nikita Gutyrchik, Nikolay Shakhpazyan, Valentina Pechnikova, Konstantin Midiber, Andrej Kontorshchikov, Elizaveta Zentsova, Lev Kakturskij

{"title":"Transthyretin Amyloidosis-One of the Causes of Heart Failure in Patients with Severe Clinical Course of COVID-19.","authors":"Zarina Gioeva, Liudmila Mikhaleva, Nikita Gutyrchik, Nikolay Shakhpazyan, Valentina Pechnikova, Konstantin Midiber, Andrej Kontorshchikov, Elizaveta Zentsova, Lev Kakturskij","doi":"10.3390/ijms26199806","DOIUrl":"10.3390/ijms26199806","url":null,"abstract":"Wild-type transthyretin amyloidosis is an underdiagnosed condition that significantly contributes to mortality in the elderly population. This histopathological study describes autopsy findings in patients with severe clinical course of COVID-19 and ATTR not identified during life. Autopsy findings in the myocardium were analyzed in 19 patients with pre-existing ATTR who died from severe COVID-19. RT PCR was used for pre- and post-mortem detection of SARS-CoV-2 RNA. Immunohistochemical typing was performed with a broad panel of antibodies against different amyloid types. Autopsy specimens from the myocardium and lungs were positive for SARS-CoV-2 RNA in 10 (53%) cases. Microscopic examination of the myocardium revealed focal cardiosclerosis and cardiomyocyte dissociation in 15 (68%) cases, hypertrophy and atrophy of cardiomyocytes in 17 (77%) and 7 (32%), respectively, and myocarditis in 4 (18%) cases. Immunohistochemical analysis determined ATTR amyloidosis in all cases. In patients with rapidly progressive heart failure, the postmortem examination revealed multiple sites of interstitial amyloid deposits and focal cardiosclerosis in the myocardium. Pre-existing cardiac amyloidosis contributes to the aggressive clinical course of COVID-19. Coupled with the toxic effect of the SARS-CoV-2 virus on the myocardium, the disease may lead to progressive heart failure and poor outcomes.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Innovative Immunotoxin Design Against Allergy Based on the IL-33 Cytokine and the Ribotoxin α-Sarcin. 基于IL-33细胞因子和核糖素α-Sarcin的新型抗过敏免疫毒素设计

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199827

Javier Narbona, Rodrigo Lázaro-Gorines, Adrián Gutiérrez-Carmona, Juan Carlos López-Rodríguez, Mayte Villalba, Javier Lacadena

{"title":"An Innovative Immunotoxin Design Against Allergy Based on the IL-33 Cytokine and the Ribotoxin α-Sarcin.","authors":"Javier Narbona, Rodrigo Lázaro-Gorines, Adrián Gutiérrez-Carmona, Juan Carlos López-Rodríguez, Mayte Villalba, Javier Lacadena","doi":"10.3390/ijms26199827","DOIUrl":"10.3390/ijms26199827","url":null,"abstract":"Allergies constitute one of the major health problems worldwide, increasing their prevalence in developed countries. To overcome this multifactorial disease, immunotherapy and the use of immune molecules, such as immunotoxins, have arisen as promising therapeutic tools. We have designed, produced, and characterized a new immunotoxin called IL-33αS, encompassing the murine IL-33 (mIL-33) as the target domain and the ribotoxin α-sarcin as the toxic domain. IL-33 is a widely described alarmin that binds to the ST2 receptor of a variety of immune cells, including ILC2s, leading to Th2-derived inflammatory response, as occurs in allergic reactions. Both IL-33αS and mIL-33 were successfully produced in the methylotrophic yeast Pichia pastoris and purified to homogeneity through affinity chromatography for their characterization. Both IL-33αS and mIL-33 were able to specifically bind to ST2+ Raw 264.7 cells, and IL-33αS kept the ribonucleolytic activity of α-sarcin, allowing IL-33αS to exhibit cytotoxic effects against ST2+-targeted cells. In addition, IL-33αS induced significantly less secretion of the Th2-linked cytokine IL-13 in comparison to mIL-33, suggesting steric interference produced by the presence of the α-sarcin. These results assess the potential therapeutic effect of this new immunotoxin against allergies, causing ST2-targeted cytotoxicity while avoiding the Th2 cytokine secretion.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antiproliferative and Proapoptotic Effects of Chetomin in Human Melanoma Cells. Chetomin在人黑色素瘤细胞中的抗增殖和促凋亡作用。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199835

Laura Jonderko, Anna Choromańska

{"title":"Antiproliferative and Proapoptotic Effects of Chetomin in Human Melanoma Cells.","authors":"Laura Jonderko, Anna Choromańska","doi":"10.3390/ijms26199835","DOIUrl":"10.3390/ijms26199835","url":null,"abstract":"Melanoma is an aggressive malignancy with poor prognosis in advanced stages, and current therapeutic options provide only limited benefits, highlighting the need for novel treatments. Chetomin, a fungal metabolite isolated from Chaetomium cochliodes, has been reported to exhibit diverse biological activities, yet its effects on melanoma cells remain poorly understood. In this study, we evaluated the antitumor potential of chetomin using the human A375 melanoma cell line. Cell viability was assessed with MTT and CellTiter-Glo® assays, which revealed a significant dose- and time-dependent reduction in proliferation following chetomin exposure. Apoptotic effects were confirmed through Annexin V staining, and immunocytochemical analysis demonstrated a concentration-dependent increase in cleaved PARP1, indicating activation of programmed cell death pathways. Collectively, these findings demonstrate that chetomin effectively inhibits melanoma cell growth and promotes apoptosis. The results suggest that chetomin represents a promising lead compound for melanoma therapy, warranting further investigation into its precise molecular mechanisms.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cinnamaldehyde Inhibits Leptin-Induced MMP-1 by Modulating Leptin Receptor/STAT3 and Blocking RhoA/NF-κB Pathways in Human Intervertebral Disc Stem Cells. 肉桂醛通过调节瘦素受体/STAT3和阻断RhoA/NF-κB通路抑制人椎间盘干细胞中瘦素诱导的MMP-1。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199819

Kuo-Feng Hua, Hsin-Chiao Yu, Hsien-Ta Hsu

{"title":"Cinnamaldehyde Inhibits Leptin-Induced MMP-1 by Modulating Leptin Receptor/STAT3 and Blocking RhoA/NF-κB Pathways in Human Intervertebral Disc Stem Cells.","authors":"Kuo-Feng Hua, Hsin-Chiao Yu, Hsien-Ta Hsu","doi":"10.3390/ijms26199819","DOIUrl":"10.3390/ijms26199819","url":null,"abstract":"Obesity is a recognized risk factor for intervertebral disc (IVD) degeneration, a condition characterized by the progressive loss of extracellular matrix components in the nucleus pulposus. Elevated circulating leptin levels in obese individuals contribute to this degeneration by upregulating matrix metalloproteinase-1 (MMP-1) expression. Targeting MMP-1 expression with low-toxicity natural compounds may provide a promising strategy to prevent or mitigate IVD degeneration. In this study, we examined the effects of cinnamaldehyde (CA), a natural compound derived from Cinnamomum osmophloeum Kaneh, on leptin-induced MMP-1 expression in human IVD cartilage endplate-derived stem cells (SV40 cell line). Our results showed that leptin induced MMP-1 expression via activation of leptin receptor-mediated JAK2/STAT3, JAK2/RhoA/STAT3, and RhoA/ERK1/2/NF-κB signaling pathways. CA significantly reduced MMP-1 expression by inhibiting phosphorylation of the leptin receptor and STAT3 and blocking RhoA and NF-κB activation, without affecting JAK2 and ERK1/2 phosphorylation. These findings suggest that CA suppresses leptin-induced MMP-1 expression by modulating specific signaling pathways, highlighting its potential as a therapeutic agent for IVD degeneration associated with obesity.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

P2Y₂ Receptor Signaling in Health and Disease. P2Y2受体在健康和疾病中的信号传导。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199815

Fatemeh Salarpour, Jean Sévigny

{"title":"P2Y2 Receptor Signaling in Health and Disease.","authors":"Fatemeh Salarpour, Jean Sévigny","doi":"10.3390/ijms26199815","DOIUrl":"10.3390/ijms26199815","url":null,"abstract":"P2Y2 receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues-including the brain, lungs, heart, and kidneys-and play pivotal roles in inflammation, wound healing, and cell migration. Through coupling with various G proteins, P2Y2 receptors initiate diverse intracellular signaling pathways that mediate calcium mobilization, cytokine release, and cytoskeletal reorganization. Recent studies highlight their dual roles in health and disease. In physiological contexts, P2Y2 receptors contribute to immune modulation and tissue repair. In pathological conditions, they are implicated in Alzheimer's disease by promoting non-amyloidogenic processing of amyloid precursor protein and in dry eye disease by enhancing mucin secretion while modulating ocular inflammation. They also influence chloride secretion and mucosal hydration in cystic fibrosis and contribute to inflammatory regulation and epithelial repair in inflammatory bowel disease. Additionally, P2Y2 receptors modulate breast cancer progression by regulating cell adhesion, migration, and matrix remodeling. Their involvement in blood pressure regulation via epithelial sodium channel modulation and their facilitative role in HIV-1 entry further underscore their clinical significance. These multifaceted functions position P2Y2 receptors as promising therapeutic targets for diverse diseases, warranting further investigation for translational applications.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0