Jian Liu, Boning Liu, Enzhi Fan, Han Zhang, Zhonglai Yin, Shuquan Lv, Weibo Wen, Feitian Min, Zhongyong Zhang, Huantian Cui
{"title":"Qianshi Mixture Treats Diabetic Nephropathy by Regulating Lipid Metabolism Reprogramming and Inhibiting Oxidative Stress Damage","authors":"Jian Liu, Boning Liu, Enzhi Fan, Han Zhang, Zhonglai Yin, Shuquan Lv, Weibo Wen, Feitian Min, Zhongyong Zhang, Huantian Cui","doi":"10.1111/jcmm.70628","DOIUrl":"https://doi.org/10.1111/jcmm.70628","url":null,"abstract":"<p>Diabetic nephropathy (DN) is a major complication of diabetes that can advance to end-stage renal disease, posing a substantial health risk. The Qianshi Mixture (QSM) has shown therapeutic potential for DN; however, its pharmacological mechanisms remain insufficiently understood. We developed a DN model in mice and administered QSM as an intervention. To assess QSM's therapeutic effects, we measured the renal-function-related biochemical indicators and examined kidney pathological changes. We then applied transcriptomics and non-targeted metabolomics to explore QSM's impact on gene expression and metabolic products within DN mice renal tissues. Based on our multi-omics analysis, the effect of QSM on lipid-metabolism-related protein expression was confirmed by western blot in kidney tissue. Additionally, we evaluated the antioxidant and anti-apoptotic properties of QSM by measuring oxidative stress indicators. QSM intervention improved hyperglycemia and proteinuria in DN mice. It also reduced key markers of renal dysfunction whilst alleviating pathological changes in kidney tissue. Through transcriptomic and metabolomic analyses, we identified that QSM affected genes and metabolites involved in lipid metabolism pathways. Notably, differentially expressed genes included <i>Ces2h</i>, <i>Ces1f</i> and <i>Alox5</i>, whilst metabolites such as EPA, 9-Oxo-ODE and LPC (20:3) were altered. Further validation revealed that QSM increased the protein levels of CES2H and CES1F whilst decreasing the expression of FABP1, CD36, ALOX15 and ALOX5. Additionally, QSM reduced oxidative stress markers. QSM inhibited both oxidative stress and apoptosis in kidney tissues. QSM protects renal tissues in DN, likely through the regulation of lipid metabolism and the mitigation of oxidative stress damage.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaolin Xie, Si Zhao, Rui Fang, Huan Chen, Han Zhang, Xue Wang, Jun Gao, Yan Liu, Zihao Cai, Ming Zhang, Bing Xu, Yuzheng Zhuge
{"title":"Vitamin E Inhibits Oxidative Stress and Inflammation in Stress-Induced Gastritis via Modulating Nrf2 and NF-κB Signalling Pathways","authors":"Xiaolin Xie, Si Zhao, Rui Fang, Huan Chen, Han Zhang, Xue Wang, Jun Gao, Yan Liu, Zihao Cai, Ming Zhang, Bing Xu, Yuzheng Zhuge","doi":"10.1111/jcmm.70463","DOIUrl":"https://doi.org/10.1111/jcmm.70463","url":null,"abstract":"<p>The incidence of stress-induced gastritis is gradually increasing. Vitamin E (VE) is widely used in inflammatory diseases due to its efficient antioxidant and anti-inflammatory effects. Here, we investigated the protective role of VE on stress-induced gastritis and its potential mechanisms. Mice were subjected to high-intensity stress caused by the forced swim test (FST) and gavaged with VE (300 mg/kg) at different time points. The results showed that VE significantly alleviated stress-induced gastric mucosal injury and related histopathological changes. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 (Hmox1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) were upregulated in the administrated groups, while the nuclear factor kappa B (NF-κB) signalling pathway was inhibited, manifested as the expression level of p-NF-κB p65 protein decreased. Furthermore, VE reduced the infiltration of macrophages in gastric tissue, followed by a synchronous decrease in the expression level of interleukin-1 beta (IL-1β) protein. Importantly, the detection of cell death by TUNEL assay and SYTOX green staining demonstrated that VE reduced cell death of gastric tissue and subsequently downregulated the pro-apoptotic factor BCL2-associated X Protein (Bax). Hence, our study suggested that VE has an outstanding preventive and therapeutic effect on stress-induced gastritis via promoting Nrf2 and inhibiting NF-κB signalling.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Pietraszek-Gremplewicz, Joanna Olszańska, Mikołaj Domagalski, Aleksandra Simiczyjew, Magdalena Kot, Aneta Skoniecka, Agata Tymińska, Michał Pikuła, Dorota Nowak
{"title":"Response of Primary Human Adipocytes to Fatty Acid Treatment","authors":"Katarzyna Pietraszek-Gremplewicz, Joanna Olszańska, Mikołaj Domagalski, Aleksandra Simiczyjew, Magdalena Kot, Aneta Skoniecka, Agata Tymińska, Michał Pikuła, Dorota Nowak","doi":"10.1111/jcmm.70622","DOIUrl":"https://doi.org/10.1111/jcmm.70622","url":null,"abstract":"<p>Obesity, nowadays a common disease, due to its complexity can cause many other disorders. In this study, a model of preadipocytes isolated from human adipose tissue was used. Cells after differentiation were additionally fattened with fatty acids such as palmitic, oleic and linoleic. Compared to control cells, obtained cells constitute a strongly reliable research model that mimics obesity occurring in humans. Achieved results have shown that adipocytes treated with fatty acids exhibited a greater number of both ‘large’ and ‘small’ lipid droplets, and an increase in lipid droplet formation and maintenance-related proteins, elevated expression of genes encoding proteins involved in the transport of fatty acids and raised secretion of cholesterol and glutamate. Fattening has also resulted in changes in the phenotype of vimentin filaments and actin cytoskeleton reorganisation. Finally, it has also been observed that hypertrophy of adipocytes was accompanied by modifications in cell metabolism, phenotypic and quantitative changes in mitochondria with a simultaneous downregulation of genes involved in mitochondrial fusion. In summary, the human research model that we propose allowed us to demonstrate several adjustments in cells mimicking the obesity state, which may contribute to expanding knowledge about obesity and improving treatment strategies for this disease.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anwar Mohammad, Jehad Abubaker, Sulaiman K. Marafie, Eman AlShawaf, Hamad Ali, Fahd Al-Mulla
{"title":"Structural Modelling of Krüppel-Like Factor 15 Zinc Finger Binding Domain to DNA Using AlphaFold 3.0: Potential Therapeutic Target for Type 2 Diabetes","authors":"Anwar Mohammad, Jehad Abubaker, Sulaiman K. Marafie, Eman AlShawaf, Hamad Ali, Fahd Al-Mulla","doi":"10.1111/jcmm.70565","DOIUrl":"https://doi.org/10.1111/jcmm.70565","url":null,"abstract":"<p>Krüppel-like factor 15 (KLF15) is a transcription factor contributing to the pathophysiology of multiple diseases, including metabolic syndromes. It is 416 residues long, with a C2H2-type zinc finger (ZnF) domain that binds to GC-rich regions regulating transcription. The role of KLF15 in glucogenesis and glucose level maintenance is well established. However, the DNA interaction mechanism at the atomic level remains unresolved. Here, we utilised computational structural biology tools to address this knowledge gap. The KLF15 ZnF–domain interacting with DNA was modelled with AlphaFold 3.0. Alanine substitution of the KLF15 ZnF domain–DNA complex revealed that residues K334A, R334A, Y332A and R392A significantly affect the binding affinities (ΔΔG) to DNA. To understand the conformational stability and dynamics of the KLF15 ZnF–domain complexes, 100-ns molecular dynamics simulations were performed. Additionally, molecular mechanics-generalised Born (MM/GBSA) surface area was utilised to calculate total binding energies. The binding energies of the wild-type KLF15 ZnF domain (−94.0 ± 0.17 kcal/mol) demonstrated a more robust binding affinity to DNA than K334A (−30.4 ± 0.35 kcal/mol), R344A (−42.8 ± 0.37 kcal/mol), Y332A (−47.7 ± 0.42 kcal/mol) and R392A (−30.8 ± 0.30 kcal/mol). The findings highlighted the unstable dynamics of the alinine substituted resdiues that consequently reduce the binding free energy compared to the wild-type KLF15 ZnF domain. In conclusion, the four identified residues are essential to recognise KLF15 ZnF DNA binding and can be considered potential hotspots for the therapeutics development for type 2 diabetes.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Neurogenic Abnormities of Paraspinal Muscles Lead to Asymmetry of Fibre Types in Adolescent Idiopathic Scoliosis","authors":"Tianyuan Zhang, Bin Li, Wenyuan Sui, Xiexiang Shao, Yaolong Deng, Zifang Zhang, Jingfan Yang, Zifang Huang, Sheng Li, Xin Fu, Wenjun Yang, Junlin Yang, Ping Hu","doi":"10.1111/jcmm.70619","DOIUrl":"https://doi.org/10.1111/jcmm.70619","url":null,"abstract":"<p>The aetiology of adolescent idiopathic scoliosis (AIS) is not clear, and may involve disorders in multiple systems. This study aims to perform the morphological and molecular analysis of neuromuscular junctions (NMJs) and explore the asymmetry of paraspinal muscles in AIS. We collected paraspinal muscles from AIS patients during surgery and also enrolled congenital scoliosis (CS) and non-scoliosis patients as controls. We performed immunofluorescence staining of NMJs for morphological analysis. Then, we extracted NMJs regions for further validation at the molecular level. We also explored the neurogenic abnormalities in the convex side and compared the asymmetry of paraspinal muscles. Morphological analysis of NMJs showed that the nerve terminal-related variables in the convex side were significantly decreased. The expression of denervation markers was increased in the synapse-rich regions. The expression of denervation markers in the convex paraspinal muscles was also significantly increased. Compared with CS and non-scoliosis patients, paraspinal muscles of AIS exhibited the transformation of fibre types, characterised by an increase in the proportion of type I fibres in the convex side. The phenomenon of fibre-type grouping was also noted, confirming the presence of neurogenic abnormalities. This study first investigated the morphological and molecular disorders of NMJs in the paraspinal muscles from AIS patients. We found that the neurogenic abnormalities existed in the convex side of the paraspinal muscle, which could lead to the conversion and grouping of fibre types. This resulted in an imbalance of bilateral paraspinal muscles and might be a potential driver of scoliosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Combination of MIF Inhibitor and AEP Targeted Inhibitor to Reduce Lung Metastasis in Breast Cancer and Its Mechanism","authors":"Junsong Chen, Wenke Xu, Luyang Meng, Xin Zhang, Mengyao Lin, Sheng Zhang, Yi Liu, Fang Guo","doi":"10.1111/jcmm.70616","DOIUrl":"https://doi.org/10.1111/jcmm.70616","url":null,"abstract":"<p>Breast cancer, the most prevalent malignant tumour in women, is characterised by high metastatic potential and frequent recurrence, both of which significantly impact patient prognosis following metastasis. To address this challenge, identifying novel therapeutic target combinations is critical for improving metastatic breast cancer treatment. This study investigates the mechanism by which asparaginyl endopeptidase (AEP) regulates breast cancer metastasis. Bioinformatics analysis revealed a potential interaction between AEP and CD74, which was subsequently confirmed through co-immunoprecipitation (co-IP) experiments. Further investigations demonstrated that AEP activates ERK pathway phosphorylation via CD74 regulation, thereby enhancing epithelial-mesenchymal transition (EMT) progression and promoting breast cancer cell migration. Compared to controls, dual inhibition of AEP and CD74 effectively reduced EMT markers and the migratory capacity of cancer cells in vitro. Subsequent in vivo experiments showed that this combinatorial strategy significantly suppressed breast cancer lung metastasis in mice without observable toxicity. These findings elucidate the molecular mechanism through which AEP promotes metastasis via CD74 regulation, while validating the therapeutic efficacy and safety of dual AEP/CD74 targeting. This study provides a novel conceptual framework and potential therapeutic targets for metastatic breast cancer intervention.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phenotypic Profile of Waldenström Macroglobulinaemia B-Cells: Establishment of a Diagnosis Scoring System and Clinico-Biological Correlations","authors":"Elise Sourdeau, Clémentine Boccon-Gibod, Aurélien Corneau, Myrto Costopoulos, Clotilde Bravetti, Marine Armand, Elise Chapiro, Florence Nguyen-Khac, Frédéric Davi, Catherine Blanc, Véronique Leblond, Marine Baron, Damien Roos-Weil, Magali Le Garff-Tavernier","doi":"10.1111/jcmm.70620","DOIUrl":"https://doi.org/10.1111/jcmm.70620","url":null,"abstract":"<p>Waldenström Macroglobulinaemia (WM) is sometimes difficult to differentiate from marginal zone lymphoma (MZL), two entities with overlapping features for which no single marker assessed by multiparameter flow cytometry (MFC) is specific. The aim of this work was to establish a diagnostic phenotypic score for bone marrow (BM) and peripheral blood (PB) WM samples, to differentiate it from MZL and to improve the detection of small circulating WM clones. This study revealed a distinct phenotypic profile between WM and MZL B-cells. WM B-cells showed decreased expression of CD19, FMC7, CD22, CD27 and increased expression of CD79b and CD13. Supervised and unsupervised MFC analyses were used to define a phenotypic scoring system: a score of 3/6 or greater in BM or 4/7 or greater in PB samples supported the diagnosis of WM (sensitivity of 97.9% and 94.1% and specificity of 80.0% and 93.5%, respectively). These results were validated in a prospective cohort with very high sensitivity and specificity for the two scoring systems. Clinico-biological correlations showed that the absence or low expression of CD38 on BM WM B-cells was significantly associated with increased BM and PB infiltration (<i>p</i> < 0.0001 and <i>p</i> = 0.0024 respectively) and <i>CXCR4</i> mutation (<i>p</i> < 0.0001). These results demonstrate that MFC can be used to differentiate WM from MZL with a scoring system that can be easily implemented in routine practice.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Matrine Inhibits the Wnt3a/β-Catenin Signalling to Attenuate Pressure Overload-Induced Atrial Remodelling and Vulnerability to Atrial Fibrillation","authors":"Guoxin Zhang, Xue Dong, Boxuan Sun, Zijun Zhou, Yinli Xu, Yuting Huang, Shan Meng, Zijun Cao, Nana Qin, Yan Zhu, Liming Yu, Huishan Wang","doi":"10.1111/jcmm.70617","DOIUrl":"https://doi.org/10.1111/jcmm.70617","url":null,"abstract":"<p>Atrial fibrillation (AF) is closely associated with atrial electrical and structural remodelling, yet effective drug strategies remain limited. Matrine (MAT), the active compound in <i>Sophora flavescens</i>, has shown anti-AF effects, but its mechanisms are unclear. This study explored MAT's impact on pressure overload-induced AF using clinical samples, bioinformatics, network pharmacology and murine models, focusing on the canonical Wnt signalling. A murine pressure overload model was established via transverse aortic constriction (TAC) surgery for 4 weeks. Programmed electrical stimulation, langendorff perfusion, echocardiography, Masson's trichrome staining and western blotting were used to evaluate the potential effects and mechanisms of MAT. The results demonstrated that TAC-induced atrial electrical and structural remodelling significantly increased susceptibility to AF in mice while also up-regulated atrial Wnt3a/β-catenin signalling as well as markers for remodelling and inflammation, which were partially supported by clinical samples. MAT dose-dependently mitigated atrial structural and electrical remodelling. Furthermore, MAT intervention inhibited Wnt3a/β-catenin signalling. However, co-administration of SKL2001, a Wnt/β-catenin agonist, counteracted MAT's benefits. The overall findings suggest that MAT treatment may serve as a potential therapeutic approach for inhibiting TAC-induced atrial electrical and structural remodelling by suppressing Wnt3a/β-catenin signalling pathways, thereby reducing susceptibility to AF.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing Cellular Immunotherapy for EBV-Associated Malignancies: Current Advances and Future Directions","authors":"Yang Gao, Di Wang, Chunrui Li","doi":"10.1111/jcmm.70603","DOIUrl":"https://doi.org/10.1111/jcmm.70603","url":null,"abstract":"<p>Standard treatments for EBV-associated malignancies, such as chemotherapy and radiotherapy, demonstrate limited efficacy in relapsed or refractory cases, underscoring an urgent need for innovative therapeutic strategies. Recent advances in immunotherapy—particularly EBV-specific cytotoxic T lymphocytes and dendritic cell vaccines—have shown promise for both treatment and prevention. Engineered T cell therapies, including T-cell receptor (TCR) and chimeric antigen receptor (CAR) approaches targeting EBV antigens such as LMP1 and gp350, are progressing in clinical development. Compared to conventional intensive therapies, which often require prolonged administration and are associated with significant toxicity, cellular immunotherapy offers a favourable safety profile alongside robust in vivo T cell expansion and potent antitumor effects. Although preclinical and clinical trial results are encouraging, further refinement of therapeutic protocols is critical to enhance efficacy and improve access for diverse patient populations. In this review, we summarise the rationale for EBV-directed cellular therapies, outline their clinical applications to date, and discuss current limitations as well as emerging opportunities to optimise these strategies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandra Margielewska-Davies, Matthew Pugh, Eszter Nagy, Ciara I. Leahy, Maha Ibrahim, Eanna Fennell, Aisling Ross, Jan Bouchal, Lauren Lupino, Matthew Care, Reuben Tooze, Gary Reynolds, Zbigniew Rudzki, Wenbin Wei, William Simmons, Vikki Rand, Kelly Hunter, John J. Reynolds, Grant S. Stewart, Katerina Bouchalova, Iona J. Douglas, Katerina Vrzalikova, Paul G. Murray
{"title":"The Overexpression of Collagen Receptor DDR1 is Associated With Chromosome Instability and Aneuploidy in Diffuse Large B-Cell Lymphoma","authors":"Sandra Margielewska-Davies, Matthew Pugh, Eszter Nagy, Ciara I. Leahy, Maha Ibrahim, Eanna Fennell, Aisling Ross, Jan Bouchal, Lauren Lupino, Matthew Care, Reuben Tooze, Gary Reynolds, Zbigniew Rudzki, Wenbin Wei, William Simmons, Vikki Rand, Kelly Hunter, John J. Reynolds, Grant S. Stewart, Katerina Bouchalova, Iona J. Douglas, Katerina Vrzalikova, Paul G. Murray","doi":"10.1111/jcmm.70318","DOIUrl":"https://doi.org/10.1111/jcmm.70318","url":null,"abstract":"<p>Although chronic inflammation is implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), the mechanisms responsible are unknown. We demonstrate that the overexpression of the collagen receptor, DDR1, correlates with reduced expression of spindle checkpoint genes, with three transcriptional signatures of aneuploidy and with a higher frequency of copy number alterations, pointing to a potential role for DDR1 in the acquisition of aneuploidy in DLBCL. In support of this, we found that collagen treatment of primary germinal centre B cells transduced with DDR1, not only partially recapitulated the aberrant transcriptional programme of DLBCL but also downregulated the expression of CENPE, a mitotic spindle that has a crucial role in preventing chromosome mis-segregation. CENPE expression was also downregulated following DDR1 activation in two B-cell lymphoma lines and was lost in most DDR1-expressing primary tumours. Crucially, the inhibition of CENPE and the overexpression of a constitutively activated <i>DDR1</i> were able to induce aneuploidy in vitro. Our findings identify a novel mechanistic link between DDR1 signalling and chromosome instability in B cells and provide novel insights into factors driving aneuploidy in DLBCL.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 10","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}