Cellular signalling最新文献

{"title":"Curcumin chemo-sensitizes intrinsic apoptosis through ROS-mediated mitochondrial hyperpolarization and DNA damage in breast cancer cells.","authors":"Esha Sarkar, Akanksha Kotiya, Rajabrata Bhuyan, Syed Tasleem Raza, Aparna Misra, Rumana Ahmad, Abbas Ali Mahdi","doi":"10.1016/j.cellsig.2025.111637","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.111637","url":null,"abstract":"<p><strong>Background: </strong>Curcumin (CUR), a polyphenol phyto-compound extracted from turmeric rhizome (Curcuma longa), suppresses cancer by inducing apoptosis while also limiting cell survival and proliferation. This in vitro and in silico research work focuses on the synergistic sensitization of Doxorubicin (DOXO) on regulating ROS-mediated apoptosis of the breast cancer cells (MDA-MB-231 and MCF-7) in DOXO-CUR co-treatment. We observed dose-dependent cytotoxicity, increased ROS production, and mtDNA fragmentation by reduced membrane potential. The combined molecular docking of Bcl2, Bax, and Caspase3 proteins with DOXO and CUR with lower binding energies proves the stable interactions of protein-ligand complexes in the combination doses.</p><p><strong>Methodology: </strong>Cell survival was measured by MTT and flow cytometry assays. Mitochondrial ROS production, mtDNA condensation, and MMP depletion were documented using fluorescence micrographs. The enrichment analysis of the ROS pathway genes by RT-qPCR (relative fold change) indicates the activation of Caspase3-mediated intrinsic apoptosis. Autodock 4.2 and Gromac 2022.4 were performed for in silico binding interaction and stability analysis.</p><p><strong>Result & conclusion: </strong>Our study calculates the DOXO and CUR combination (0.33 + 33 μM in MDA-MB-231 and 0.14 + 14 μM in MCF-7) shows maximum growth inhibition (70-75 %) by elevated oxidative stress and reduced membrane potential, which suggests that CUR could be a potential therapeutic agent for treating breast cancers in near future. The method of apoptosis was further analyzed, where elevated cellular ROS level by CUR + DOXO combination therapy depleted mitochondrial membrane potential and enhanced the DNA condensation. The mitochondrial pro-apoptotic genes BAX, BAK, BIM, CASPASE9, and CASPASE3 and anti-apoptotic BCL2 gene expressions depicted triggering intrinsic apoptosis pathway, co-relating with the in silico molecular docking, simulation, and MM-PBSA energy calculations. The synergism between CUR and DOXO was also validated by increased binding affinity and reduced inhibitory constant against key proteins Bcl2, Bax, and Caspase3. Bcl2-DOXO showed BE: -5.03 and Bcl2-DOXO-CUR showed BE: -4.7. Whereas, Bax-DOXO binding energy was -5.49 and Bax-DOXO-CUR binding was -3.83. The most preferable synergistic binding was found with Caspase3 protein, where Caspase3-DOXO docking energy was -1.63 but Caspase3-DOXO-CUR combined docking energy was -3.51. The stability of protein-ligand complexes was accessed with MD simulations and binding free energy calculations, Bcl2-CUR-DOXO combination complex showed ∆G: -25.62, Bax-DOXO-CUR complex showed the maximum ∆G: -34.18, with Caspase-CUR-DOXO complex (∆G: -15.18), indicating the proteins most stable conformation while interacting with CUR + DOXO combination. The correlation between the in vitro and in silico analysis of apoptosis pathway components widens the further research scope for ","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111637"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircHOMER1 promotes silica-induced pulmonary fibrosis by binding to HuR and stabilizing NOX4 mRNA.","authors":"Qiuyun Wu, Qianyi Zhang, Chunmeng Jin, Xue Liu, Hongmin Yu","doi":"10.1016/j.cellsig.2025.111638","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.111638","url":null,"abstract":"<p><strong>Background: </strong>Silicosis, one of the serious occupational diseases, is mainly manifested by pulmonary fibrosis induced by long-term exposure to silica particles in workplace. Evidence demonstrates that circular RNAs (circRNAs) are interesting regulators of pulmonary fibrosis process. So, further elucidation of the role of circRNAs may provide a new perspective into mechanisms driving pulmonary fibrosis and silicosis.</p><p><strong>Methods: </strong>The characteristics of circRNA homer scaffold protein 1 (hsa_circ_0006916, circHOMER1) was assessed using Actinomycin D, RNase R, and nucleoplasmic separation assay. The histopathological examination and Enzyme-linked immunosorbent assay (ELISA) were used to confirm circHOMER1 function in mouse lung tissues under silica particle exposure. The expression of circHOMER1, human antigen R (HuR) and NADPH oxidase 4 (NOX4) was identified by western blot or RT-qPCR assay. The RNA immunoprecipitation (RIP) assay and plasmid co-transfection were used to analyze the interaction between circHOMER1, HuR and NOX4.</p><p><strong>Results: </strong>We confirmed an upregulated circHOMER1 in silicosis fibrosis. Functional assays showed that the knockdown of circHOMER1 suppressed the viability of fibroblasts and the production of fibrotic molecules and alleviated the histology fibrotic changes in lung tissues from mouse exposed to silica particles. Mechanistically, we found that circHOMER1 directly bound to HuR and promoted its protein expression in fibroblasts. And, circHOMER1 further regulated HuR/NOX4 signaling axis through HuR to stabilize NOX4 mRNA, which enhanced the production of reactive oxygen species (ROS), thereby promoting the silicosis fibrosis process.</p><p><strong>Conclusion: </strong>This study revealed the role of circHOMER1 in silica-induced pulmonary fibrosis, suggesting that the inhibition of circHOMER1 may be a potential therapeutic approach to relieve the pathological process of silicosis.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111638"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant roles of RNA 5-methylcytosine methylation in cancer","authors":"Na Lou ,&nbsp;Xinyu Gu ,&nbsp;Leiya Fu ,&nbsp;Juan Li ,&nbsp;Chen Xue","doi":"10.1016/j.cellsig.2024.111529","DOIUrl":"10.1016/j.cellsig.2024.111529","url":null,"abstract":"<div><div>Cancer stands as a leading cause of mortality and poses an escalating threat to global health. Epigenetic dysregulation is pivotal in the onset and advancement of cancer. Recent research on RNA 5-methylcytosine (m⁵C) methylation has underscored its significant role in cancer. RNA m⁵C methylation is a key component in gene expression regulation and is intricately linked to cancer development, offering valuable insights for cancer diagnosis, treatment, and prognosis. This review provides an in-depth examination of the three types of regulators associated with RNA m⁵C methylation and their biological functions. It further investigates the expression and impact of RNA m⁵C methylation and its regulators in cancer, focusing on their mechanisms in cancer progression and clinical relevance. The current research on inhibitors targeting RNA m⁵C methylation-related regulators remains underdeveloped, necessitating further exploration and discovery.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"126 ","pages":"Article 111529"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Game-changing breakthroughs to redefine the landscape of the renin–angiotensin–aldosterone system in health and disease","authors":"Pitchai Balakumar ,&nbsp;Gowraganahalli Jagadeesh","doi":"10.1016/j.cellsig.2024.111459","DOIUrl":"10.1016/j.cellsig.2024.111459","url":null,"abstract":"<div><div>Novel perspectives on the role of the renin–angiotensin–aldosterone system (RAAS) offer a groundbreaking understanding of the system's role in health and illness. Our understanding of the role of the RAAS in several diseases, such as heart failure, hypertension, metabolic disorders, and chronic renal disease, has been broadened by recent studies. Specific variations in RAAS pathways can affect the course of disease and response to treatment, as shown by genetic and molecular research. The dynamic and fast-evolving nature of RAAS research described in this special issue might transform our approach to managing renal, neurological, and cardiovascular health, among other disease conditions, including cancer.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"126 ","pages":"Article 111459"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nintedanib improves bleomycin-induced pulmonary fibrosis by inhibiting the Clec7a/SPP1 pathway in interstitial macrophages","authors":"Zuoquan Zhong ,&nbsp;Yefei Gao ,&nbsp;Chunxiao He ,&nbsp;Weijie Li ,&nbsp;Le Sang ,&nbsp;Yunlei Huang ,&nbsp;Xing Chen ,&nbsp;Mengyao Xie ,&nbsp;Chu Zhang ,&nbsp;Yuefang Yu ,&nbsp;Ting Zhu ,&nbsp;Jian Sun","doi":"10.1016/j.cellsig.2025.111635","DOIUrl":"10.1016/j.cellsig.2025.111635","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a terminal lung disease with high mortality rate. Although Nintedanib (Nin) is an effective treatment for IPF, its precise mechanism of action remains unclear. In this study, we performed an integrated analysis of single-cell sequencing and RNA-seq data from lung tissues of both fibrotic and Nin-treated fibrotic mice to uncover new therapeutic mechanisms of Nin in IPF. Our results revealed an increase in interstitial macrophages following bleomycin (BLM) treatment. We used Monocle2, Cellchat, and in vivo experiments to demonstrate that Nin can inhibit Clec7a in interstitial macrophages, thereby suppressing the SPP1-mediated profibrotic pathway. Additionally, we utilized Scenic to predict transcription factors and identified NFκB as a major transcription factor in interstitial macrophages. In the in vitro experiments, we found that inhibiting Clec7a improved the secretion of SPP1 by M2 macrophages through the NFκB pathway. In subsequent in vivo experiments, we found that inhibiting of Clec7a improves pulmonary fibrosis through the NFκB/SPP1 pathway, and Nin alleviated BLM-induced pulmonary fibrosis by inhibiting Clec7a in interstitial macrophages. In summary, our study indicates that interstitial macrophages are upregulated in pulmonary fibrosis, and Nin reduces fibrosis by inhibiting Clec7a in interstitial macrophages, which in turn diminishes the NFκB /SPP1 pathway. These findings provided a new perspective on the mechanism of action of Nin in treating pulmonary fibrosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"128 ","pages":"Article 111635"},"PeriodicalIF":4.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT5 -mediated desuccinylation of UQCRC2 attenuates osteogenic differentiation of aged BM-MSCs through impairing mitochondrial homeostasis.","authors":"Xin Hua Yin, Xiao Yuan Wang, Shi Chang Liu, Xu Xu Chen, Liang Yan, Liang Li, Gao Le He, Ming Yang, Zhong Kai Liu","doi":"10.1016/j.cellsig.2025.111636","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.111636","url":null,"abstract":"<p><strong>Background: </strong>The osteogenic differentiation potential of bone marrow mesenchymal stem cells (BM-MSCs) is critical for bone regeneration and repair. In recent years, the role of protein succinylation modification in regulating cellular metabolism has garnered increasing attention. However, its mechanism in osteogenic differentiation remains unclear.</p><p><strong>Methods: </strong>Oxygen consumption rate (OCR) and mitochondrial ROS (mtROS) were detected to assess mitochondrial function in BM-MSCs with successive passages. Alizarin red staining and western blot experiments were used to evaluate osteogenic differentiation capacity. .Succinylation modification omics and Co-IP detection were conducted to determine SIRT5-mediated desuccinylation of UQCRC2 .</p><p><strong>Results: </strong>Bioinformatics analysis revealed that sirtuin 5 (SIRT5) expression is upregulated with multiple rounds of BM-MSCs' passages, and is associated with biological pathways such as oxidative phosphorylation (OXPHOS), cellular senescence, and inhibition of osteogenic differentiation. Experiments in vitro confirmed the up-regulation of SIRT5 and the suppression of osteogenic differentiation with the increased times of BM-MSCs' passages. Overexpression of SIRT5 enhanced OXPHOS and elevated mtROS levels, but reduced the expression of Runx2 and osteocalcin, and decreased calcified nodules, thereby inhibiting the osteogenic differentiation of BM-MSCs. SIRT5-mediated desuccinylation of ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) at the site of K250 promoted UQCRC2 translocation from cytoplasm to mitochondria, which enhanced the activity of mitochondrial respiratory complex III. It further increased mtROS, accelerated cellular senescence and inhibited the osteogenic differentiation of BM-MSCs.</p><p><strong>Conclusion: </strong>SIRT5 reduces succinylation modification of UQCRC2, promotes mitochondrial respiration and mtROS, and thus reduces the osteogenic differentiation ability of BM-MSCs cells. SIRT5 might be a potential target to prevent the suppression of osteogenic differentiation of of BM-MSCs after multiple rounds passages.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111636"},"PeriodicalIF":4.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fibroblasts promote oral squamous cell carcinoma progression by targeting ATP7A via exosome-mediated paracrine miR-148b-3p.","authors":"Shuaiyuan Zhang, Xiaoyong Liu, Jiaqiang Zhang, Kunyi Chen, Wei Li, Yihuan Yao, Anxun Wang, Jinsong Hou","doi":"10.1016/j.cellsig.2025.111631","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.111631","url":null,"abstract":"<p><p>Cuproptosis is a newly discovered form of non-apoptotic cell death. Cancer-associated fibroblasts (CAFs) can secrete various bioactive substances, including exosomes, to promote tumor progression. However, the impact of CAFs on the regulation of copper metabolism and cuproptosis in oral squamous cell carcinomas (OSCC) has not been investigated. In the present study, we revealed that up-regulated expression of ATP7A was correlated with reduced copper abundance, advanced clinicopathological characteristics and poor prognosis in OSCC. The knockdown of ATP7A significantly increased cuproptosis and inhibited malignant progression in vitro, as well as decreased tumor growth and metastasis in vivo. Furthermore, co-culture assays and dual-luciferase reporter demonstrated that upregulated expression of ATP7A in OSCC was due to a reduction of miR-148b-3p in CAF-derived exosomes. The downregulation of miR-148b-3p was observed to significantly elevate ATP7A expression, inhibit cuproptosis and increase malignant progression in vitro. Additionally, in vivo studies demonstrated that this process promoted tumor growth and metastasis. OSCC exhibit a low level of cuproptosis due to the uptake of miR-148b-3p-depleted exosomes from CAFs, leading to a more malignant phenotype in the tumor microenvironment by targeting ATP7A. The results of our experiments suggest that targeting the miR-148b-3p/ATP7A axis might be a promising therapeutic approach for the treatment of oral cancer.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111631"},"PeriodicalIF":4.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of Hematopoietic PBX-Interacting Protein (HPIP) in trophoblast fusion and invasion: Implications in pre-eclampsia pathogenesis.","authors":"Vasudevarao Penugurti, Oindrilla Dey, Sruchytha Kalali, Deepak Kumar Kashyap, Saratchandra Singh Khumukcham, Ajnas Kizhuvedath, Sarthak Satpathy, Manjari Kiran, Anupama Row, Tarakeswari Surapaneni, Bramanandam Manavathi","doi":"10.1016/j.cellsig.2025.111633","DOIUrl":"https://doi.org/10.1016/j.cellsig.2025.111633","url":null,"abstract":"<p><p>Pre-eclampsia is a known hypertensive disorder of pregnancy. While abnormal placentation and poor trophoblast invasion into maternal endometrium during blastocyst implantation are primary causes of pre-eclampsia, the underlying mechanisms remain elusive. Hematopoietic PBX-Interacting protein (HPIP) is an estrogen receptor (ER) interacting protein that plays a pivotal role in cell proliferation, migration, and differentiation; however, its role in trophoblast functions is largely unknown. In this study, we used BeWo cells as a model system to investigate trophoblast fusion and syncytialization, focusing on the role of HPIP in regulating these critical aspects of trophoblast functions. Herein, we report that HPIP expression declines during forskolin-induced trophoblast fusion in BeWo cells. In support of these observations, HPIP depletion enhanced forskolin-induced human chorionic gonadotropin-β (β-hCG), ERVWE1, and GCM1 expression, markers for trophoblast fusion. Furthermore, silencing of HPIP decreased cell invasion and epithelial to mesenchymal transition (EMT), a prerequisite for syncytialization in BeWo cells. Functional genomic studies further revealed a regulatory role for HPIP in a subset of gene networks involved in trophoblast fusion and EMT. We also uncovered that HPIP is a proteolytic substrate of furin, which is known to promote trophoblast cell fusion. Clinical data further indicated a significantly lower expression level of HPIP in pre-eclampsia subjects than in normal subjects. These findings imply that HPIP inhibits trophoblast fusion while promoting invasion and EMT, and its downregulation in trophoblasts might have implications for pre-eclampsia development.</p>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":" ","pages":"111633"},"PeriodicalIF":4.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation-induced suppression of PRDM16 in colorectal cancer metastasis through the PPARγ/EMT pathway","authors":"Yu Wang ,&nbsp;Shuai Zheng ,&nbsp;Huabin Gao ,&nbsp;Yuting Wang,&nbsp;Yongyu Chen,&nbsp;Anjia Han","doi":"10.1016/j.cellsig.2025.111634","DOIUrl":"10.1016/j.cellsig.2025.111634","url":null,"abstract":"<div><h3>Background</h3><div>PR/SET domain 16 (PRDM16) is an important transcription factor in the differentiation process of brown adipocytes, which plays an important role in maintaining the special morphological characteristics and cellular function of brown adipocytes. However, the role of PRDM16 in human colorectal cancer (CRC) is currently unknown.</div></div><div><h3>Methods</h3><div>Methylation sequencing, methylation-specific PCR (MSP), multiple bioinformatics analyses, Co-Immunoprecipitation (Co-IP) assay and Immunofluorescence (IF) staining, in vitro and in vivo functional experiments were performed to study the biological role of PRDM16 in CRC progression.</div></div><div><h3>Results</h3><div>Our study found that methylation level of PRDM16 was associated with CRC and lung metastasis of CRC by DNA methylation sequencing. Furthermore, we identified methylation sites within the promoter region of PRDM16. PRDM16 expression was significantly lower in human CRC tissue samples and dramatically associated with tumor size, T stage, overall survival rates and disease-free survival rates of CRC patients. Down-regulation of PRDM16 significantly promoted proliferation, migration, and invasion of CRC cells by regulating EMT pathway in vitro and in vivo. Decitabine which was a methylate inhibitor increased PRDM16 expression and inhibited CRC progression in vitro and in vivo. Further study showed that PRDM16 interacted with PPAR γ in nucleus and upregulated its expression in CRC. PPAR γ expression was lower in CRC tissues compared with the adjacent colorectal mucosal tissues. PPAR γ suppressed CRC progression including proliferation, colony formation, migration and invasion via EMT pathway, but not affect PRDM16 expression. Decitabine treatment could reverse the biological effects caused by PPAR γ down-regulation in CRC cells.</div></div><div><h3>Conclusion</h3><div>Our study first shows that DNA methylation-mediated suppresser role of PRDM16 in CRC progression via PPAR γ/EMT pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111634"},"PeriodicalIF":4.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063844","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}

{"title":"HMGB1-mediated macrophage regulation of NF-κB activation and MMP3 upregulation in nucleus pulposus cells: A critical mechanism in the vicious cycle of intervertebral disc degeneration","authors":"Shixin Lu ,&nbsp;Ming Li ,&nbsp;Ziying Cheng ,&nbsp;Yuwei Liang ,&nbsp;Junshen Huang ,&nbsp;Jiajun Huang ,&nbsp;Kun Wang ,&nbsp;Dengbo Yao ,&nbsp;Enming Chen ,&nbsp;Peng Wang ,&nbsp;Yuxi Li ,&nbsp;Lin Huang","doi":"10.1016/j.cellsig.2025.111628","DOIUrl":"10.1016/j.cellsig.2025.111628","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, primarily driven by inflammatory processes within the disc, particularly involving the infiltration and activity of macrophages. High Mobility Group Box 1 (HMGB1) has been identified as a crucial mediator in this inflammatory cascade, yet its precise role in macrophage-induced disc degeneration remains unclear. In this study, we employed a combination of <em>in vivo</em> and <em>in vitro</em> models, including genetically engineered mice with macrophage-specific overexpression of HMGB1, a rat model of IVDD, and cultured macrophages and nucleus pulposus cells (NPCs), to elucidate the role of HMGB1 in IVDD. Our findings reveal that HMGB1 overexpression in macrophages significantly accelerates IVDD progression by enhancing NF-κB activation and upregulating MMP3 expression in NPCs. Furthermore, the administration of glycyrrhizin (GL), an HMGB1 inhibitor, effectively mitigated these effects, delaying IVDD progression. This study not only uncovers the critical mechanisms by which HMGB1 regulates the interactions between macrophages and NPCs in the inflammatory microenvironment but also provides a theoretical framework for targeting HMGB1 as a potential therapeutic strategy for IVDD. Thus, our findings suggest a promising novel approach for the treatment of this condition.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111628"},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}