{"title":"Diagnostic Use of CCR3, CD63, CD203c and FcεRIα on Blood Leukocytes of Allergic Asthma and Combined Allergic Rhinitis and Asthma Syndrome","authors":"Junling Wang, Mengmeng Zhan, Fangqiu Gu, Huiyun Zhang, Hua Xie, Bingyu Qin, Shaoheng He","doi":"10.1111/jcmm.70594","DOIUrl":"https://doi.org/10.1111/jcmm.70594","url":null,"abstract":"<p>Altered basophil identification markers have been discovered to associate with allergic asthma (AA) recently. However, little is known of the expressions of basophil markers in blood granulocytes. We therefore parallel tested them in peripheral blood mononuclear cell (PBMC) and granulocyte populations of patients with AA and combined allergic rhinitis and asthma (ARA) by flow cytometry and assessed their diagnostic performance and examined plasma levels of EDN, LTC<sub>4</sub> and PGD<sub>2</sub>. We found CCR3<sup>+</sup> cell numbers increased markedly in granulocytes of AA and ARA patients. Almost all isolated CCR3<sup>+</sup> PBMC were basophils, but CCR3<sup>+</sup> granulocytes contained up to 96.0% eosinophils and 12.8% basophils. The numbers of CD63, CD203c and FcεRIα expressing CCR3<sup>+</sup> granulocytes increased markedly, and the mean fluorescent intensity of CD203c, FcεRIα and CD63 expression on CCR3<sup>+</sup> granulocytes and PBMC enhanced consistently in AA and ARA patients. The area under the curve achieved the highest values for CD203c<sup>+</sup>CCR3<sup>+</sup> granulocyte numbers in AA and ARA patients. Plasma levels of EDN, LTC<sub>4</sub> and PGD<sub>2</sub> in AA and ARA patients increased and correlated well with CCR3<sup>+</sup> granulocyte numbers. In conclusion, discovering basophils in peripheral blood granulocytes provides greater scope for the clinical use of basophil tests.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315309","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":"CuATSM Enhances Wound Repair Without Scarring via Hippo/YAP Signalling Pathway to Reduce Ferroptosis and Macrophage Polarisation","authors":"Yingdan Tang, Jiazong Ye, Tingye Xu, Yuhuan Sun, Weiyang Meng, Lielie Zhu, Zhongheng Jia, Qian Wu, Daqing Chen, Fangfang Wu","doi":"10.1111/jcmm.70590","DOIUrl":"https://doi.org/10.1111/jcmm.70590","url":null,"abstract":"<p>Skin wound healing is a complex biological process involving haemostasis, inflammation, proliferation/repair and remodelling. However, skin scarring, as one of the important stages in the healing process, can adversely affect the structure and function of related organs. Currently, effective treatments to address such scars remain insufficient. In this study, we established a full-thickness skin excision wound model using male ICR mice, which were randomly divided into a Control group and a CuATSM group. The CuATSM group received CuATSM (30 mg/kg) via gavage, with daily treatments continuing throughout the observation period. The Control group received an equivalent volume of 0.9% sodium chloride solution. Wound healing progression was evaluated through macroscopic photography, histological analyses, Western blotting and quantification of relevant biochemical markers at different healing stages. Our study reveals that CuATSM not only promotes rapid skin wound healing but also reduces scar formation in the late healing phase. Furthermore, our findings suggest that this effect is mediated through the ferroptosis-induced Hippo/YAP signalling pathway and macrophage polarisation. These findings highlight CuATSM as a promising therapeutic candidate for achieving scarless wound repair in clinical applications.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 12","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300245","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":"Adipocyte RNF20 Knockout Leads to Hyperinsulinemia via the H2Bub-H3K4me3-Slc2a4 Axis","authors":"Ying Zhao, Xiaojuan Liang, Jiayu Tang, Chunwei Cao, Chunhuai Yang, Shulin Yang, Jianguo Zhao, Jinxiang Yuan, Meng Zhang, Yanfang Wang","doi":"10.1111/jcmm.70649","DOIUrl":"https://doi.org/10.1111/jcmm.70649","url":null,"abstract":"<p>The ubiquitin ligase RING finger 20 (RNF20) mediated the monoubiquitination of histone H2B at lysine 120 (H2Bub), an epigenetic modification known to regulate key biological processes such as fat tissue development, tumorigenesis, spermatogenesis and so on. Despite our previous findings showing that mice with adipocyte-specific deletion of <i>Rnf20</i> (ASKO mice) develop hyperinsulinaemia, the underlying mechanisms remain unclear. In this study, we investigated the role of adipocyte RNF20 in maintaining systemic insulin homoeostasis in ASKO mice. Our results reveal that ASKO mice exhibit an enlarged pancreas, increased islet size and a greater number of pancreatic β-cells. Fat tissue in ASKO mice showed reduced insulin sensitivity, evidenced by diminished AKT phosphorylation under basal and insulin-stimulated conditions, alongside suppressed insulin signalling pathways. Furthermore, the decreased levels of histone modifications, including H2Bub, H3K4me3 and H3K79me3, were observed in both ASKO mice fat tissues and <i>Rnf20</i>-knockdown 3T3-L1 cells. Mechanistically, <i>Rnf20</i> knockdown in adipocytes reduced H3K4me3 occupancy at the <i>Slc2a4</i> gene locus, inhibiting GLUT4 expression and inducing adipose-specific insulin resistance. These findings establish a critical role for adipocyte RNF20 in the insulin signalling regulation via the H2Bub-H3K4me3-<i>Slc2a4</i> axis, highlighting its importance in systemic glucose metabolism.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291874","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}
Bin Liu, Tingting Lu, Guangming Zhang, Xiaohua Dong, Miao Yu, Hui Cai
{"title":"LncRNA SNHG14 Regulated by ZNF460 Promotes Gastric Cancer Progression and Metastasis by Targeting the miR-206/FNDC3A Axis","authors":"Bin Liu, Tingting Lu, Guangming Zhang, Xiaohua Dong, Miao Yu, Hui Cai","doi":"10.1111/jcmm.70652","DOIUrl":"https://doi.org/10.1111/jcmm.70652","url":null,"abstract":"<p>The current study investigated the functional role of long non-coding RNA SNHG14 (lncRNA SNHG14) in gastric cancer (GC) progression and its underlying mechanisms. Compared with para-carcinoma tissues, SNHG14 was upregulated in GC tissues, correlating with a poor prognosis in GC patients. SNHG14 knockdown significantly weakened the proliferation, migration and invasion capabilities of GC cell lines while enhancing the apoptosis ability of GC cells. Simultaneously, SNHG14 overexpression reversed these effects. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation assays revealed that SNHG14 was primarily located in the cytoplasm of GC cells. Combined sequencing of the miRNAome and transcriptome depicted that miR-206 could be a potential target for SNHG14. Mechanistically, assays such as luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown established that lncRNA SNHG14 acted as a sponge for miR-206. This prevented the degradation of its target gene, FNDC3A, playing a tumour-suppressive role in GC. In addition, FNDC3A directly interacted with the SNHG14 promoter and induced transcription, thus facilitating GC progression. Therefore, our research findings suggested a novel pathway to promote GC progression through the FNDC3A/lncRNA SNHG14/miR-206/FNDC3A axis. Moreover, the findings indicated that SNHG14 could become a potential biomarker and therapeutic target for GC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291875","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":"A Model of Butyrate Activity and Resistance in CRC","authors":"Michael Bordonaro","doi":"10.1111/jcmm.70656","DOIUrl":"https://doi.org/10.1111/jcmm.70656","url":null,"abstract":"<p>Butyrate, a breakdown product of dietary fibre, may in part mediate the ability of a high-fibre diet to reduce the risk of colorectal cancer (CRC). However, CRC can still develop despite a high-fibre diet; hence, butyrate resistance may influence colonic tumorigenesis. To model butyrate resistance in vitro, butyrate-resistant cells were developed and mechanisms identified by which these cells evade the effects of butyrate. These mechanisms can be interpreted in light of the existing literature to further our understanding of butyrate resistance. The current review integrates findings from various studies from my laboratory on butyrate-resistant cells, in addition to other work in the literature, to present a model of how butyrate-resistant CRC cells balance different signalling outputs to generate the resistant phenotype. Loss of p300 expression in butyrate resistance allows increased noncanonical Wnt signalling to occur without activating differentiation pathways, AKT/PKB survival signalling is activated, and CBP-Wnt activity is maintained in the pro-proliferative range. Further, overexpression of Tcf3 suppresses butyrate-induced Wnt hyperactivation. Other factors, signalling pathways and modifying influences also affect butyrate sensitivity vs. resistance. Understanding the possible role of butyrate resistance will assist in improving chemopreventive strategies for this disease.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273392","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}
Feiyu Wei, Yazhe Ma, Hong Xiang, Xi Zhang, Jie Fan
{"title":"LncRNA Dleu2 Serve as a Novel Biomarker for Ablation Recurrence and Promote Atrial Remodelling by Targeting Nr4a1 in Atrial Fibrillation","authors":"Feiyu Wei, Yazhe Ma, Hong Xiang, Xi Zhang, Jie Fan","doi":"10.1111/jcmm.70618","DOIUrl":"https://doi.org/10.1111/jcmm.70618","url":null,"abstract":"<p>Atrial remodelling is the principal pathological mechanism for atrial fibrillation (AF) development and progression. Long noncoding RNAs (LncRNAs) exhibit important effects on cardiovascular diseases. However, the role of LncRNAs in AF development requires further investigation. This study aimed to explore the function and mechanism of LncRNAs in AF. The differentially expressed LncRNAs of atrial tissue in a mouse AF model, which was established via continuous infusion of Ang II for 3 weeks, were screened with RNA sequencing. Experiments included an electrophysiological study; Masson, H&E and TUNEL staining; flow cytometry; and RNA pull-down; FISH and RNA immunoprecipitation assays were performed to define the function and underlying mechanisms of LncRNAs in AF susceptibility and atrial remodelling. The Kaplan–Meier method was used to plot the curve of freedom from atrial tachyarrhythmia. LncRNA Dleu2 expression was increased in atrial tissue and peripheral blood and was positively associated with left atrial fibrosis in persistent AF. Furthermore, elevated expression of LncRNA Dleu2 was correlated with a higher AF recurrence rate after ablation at the 24-month follow-up (65.0% vs. 85.0%, <i>p</i> = 0.03). Accordingly, upregulation and downregulation of LncRNA Dleu2 expression could regulate atrial remodelling and AF susceptibility, and we also demonstrated that LncRNA Dleu2 directly bound to Nr4a1. Subsequently, inhibition of Nr4a1 expression could also regulate AF susceptibility and atrial remodelling and reverse the effects of LncRNA Dleu2 on AF occurrence. This study demonstrated that LncRNA Dleu2 was independently associated with atrial fibrosis and AF recurrence after ablation, and contributed to AF susceptibility by directly targeting Nr4a1.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273391","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":"Monoclonal Antibodies to Thyrotropin Receptor With Thyroid-Stimulating Activity Activate the NF-κB Pathway to Induce Chemokine Expression","authors":"Yang Yang, Chen Hui","doi":"10.1111/jcmm.70647","DOIUrl":"https://doi.org/10.1111/jcmm.70647","url":null,"abstract":"<p>The A subunit of thyrotropin receptor (TSHR) is thought to be the crucial gene mediating stimulatory autoantibodies in Graves' diease (GD), but it remains unclear what the molecular basis of this pathological antibody response is. Stimulatory TSHR autoantibodies may induce activation of multiple signalling pathways in GD, modulate chemokine exposure and further stimulate immune imbalance. In this study, we prepared TSHR 289 protein by using insect baculovirus expression, adenovirus-expressed TSHR289 immunised mice, and obtained three mouse anti-TSHR monoclonal antibodies (mAbs), 1A4, 7C3 and 22B1, by the hybridoma technique. Flow assay and ELISA tests tested the activity and competitive binding of the mAbs. After mAbs stimulation of human thyrocytes, RT-qPCR and ELISA were used to detect the expression of chemokine; Western blotting detected the expression of CCL19 and the level of phosphorylation of NF-κB. Nanogram concentrations of the IgG mAbs 1A4, 7C3 and 22B1 and their Fab induce TSHR stimulation. TRAb in the serum of GD patients competitively inhibits the binding of HRP-conjugated mAbs to TSHR on the coated plate. Injection of micrograms of 7C3 resulted in elevated serum thyroxine and columnar and papillary hyperplasia of thyroid follicular epithelial cells. All three mAbs induced distinct expression of CCL2, CCL19 and CCL5 by activating canonical and non-canonical NF-κB signalling pathways in human thyrocytes. Collectively, we obtained three mouse anti-TSHR mAbs which provide an improved approach to characterise the molecular basis of this pathological response, and confirmed that stimulating antibodies activate NF-κB, inducing chemokines involved in the autoimmune response.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264529","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":"From Growth Factors to Structure: PDGF and TGF-β in Granulation Tissue Formation. A Literature Review","authors":"Josiah Irma, Arief S. Kartasasmita, Angga Kartiwa, Irawati Irfani, Saraswati Anindita Rizki, Serena Onasis","doi":"10.1111/jcmm.70374","DOIUrl":"https://doi.org/10.1111/jcmm.70374","url":null,"abstract":"<p>Platelet-Derived Growth Factors (PDGFs) and Transforming Growth Factor β (TGFβ) are pivotal in orchestrating the complex wound healing process, particularly in granulation tissue formation. This review aims to comprehensively examine the roles of PDGF alongisde TGFβ in granulation tissue formation and their implications for abnormal wound healing. PDGFs, as homodimeric or heterodimeric combinations, such that PDGF-AA, PDGF-AB and PDGF-BB stimulate fibroblast proliferation and extracellular matrix synthesis, which is crucial for tissue repair. TGFβ, with its three isoforms, influences granulation tissue through diverse functions, with TGFβ-1 pivotal in fibrosis formation. Understanding their signalling pathways, notably PDGF's engagement with PDGF receptors and subsequent activation of cellular pathways, illuminates their roles in wound healing cascades. Excessive granulation, a complication of abnormal wound healing, involves dysregulated PDGF and TGFβ activity, leading to hypertrophic scar formation. Clinical management, particularly in ophthalmology, addresses excessive granulation's impact on procedures like endo-dacryocystorhinostomy. Strategies employing steroid agents and Mitomycin-C aim to mitigate ostium granulation. The potential use of PDGF receptor blockers, such as olaratumab, warrants further investigation for managing excessive granulation. In conclusion, PDGF and TGFβ emerge as critical regulators in granulation tissue formation, underscoring their significance in wound healing processes and offering avenues for therapeutic intervention.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255930","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":"Impact of SPP1 and HMOX1 Genes in Glioma: Correlations With Oncolytic Virus Infection, Adverse Prognosis and Increased Cell Proliferation","authors":"Chunze Cui, Chunyan Wu, Shaoqi Zhang, Xiaofeng Yin","doi":"10.1111/jcmm.70651","DOIUrl":"https://doi.org/10.1111/jcmm.70651","url":null,"abstract":"<p>A high death rate among glioma patients is primarily due to poor prognostic outcomes and tumour metastasis. Oncolytic viruses have gained attention as a potential therapeutic strategy as eliminating tumour cells and modifying tumour microenvironment. This research highlights the urgent necessity to investigate novel therapeutic targets and clarify molecular mechanisms in glioma. The GSE166914 dataset was analysed to examine the SPP1 and HMOX1 expression after VSV-M51 infection in glioma. By utilising the CancerSEA database, we assessed the potential function of SPP1/HMOX1 among pan-cancer. Analysis of gene/protein expression levels and clinical significance was performed to identify the roles of SPP1/HMOX1 using TCGA-glioma data. A correlation analysis was performed to screen co-expressed genes, followed by GSEA analysis. qPCR and HPA analysis were utilised to assess the mRNA/protein levels of SPP1 and HMOX1 in glioma tissues. The anti-apoptotic activity of SPP1 and HMOX1 was confirmed utilising the CCK-8 assay and flow cytometry. VSV-M51 infection resulted in SPP1/HMOX1 downregulation in T98 cells. The expression levels of SPP1/HMOX1 were significantly increased in glioma and associated with histological classifications and WHO grades. Elevated levels of SPP1/HMOX1 were related to poor prognosis in glioma. SPP1/HMOX1 was involved in influencing glioma cell motility through the PI3K/AKT, JAK–STAT and syndecan 1 signalling pathways. In vitro experiments showed higher expression levels of SPP1/HMOX1 in glioma tissues. Silencing SPP1/HMOX1 suppressed glioma cell proliferation and promoted apoptosis. In conclusion, dysregulated SPP1/HMOX1 expression was strongly related to glioma WHO grades and worse outcomes, providing deeper insights into glioma therapeutic targets and oncolytic virus-based treatments.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255933","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}
Peng Kang, Xiangjun Zhou, Sheng Zhao, Weimin Yu, Zehua Ye, Fan Cheng
{"title":"Inhibitors of p53 Apoptosis-Stimulating Protein Mitigate Acute Kidney Injury by Modulating the HIF-1α/SLC7A11 Pathway to Suppress Ferroptosis","authors":"Peng Kang, Xiangjun Zhou, Sheng Zhao, Weimin Yu, Zehua Ye, Fan Cheng","doi":"10.1111/jcmm.70580","DOIUrl":"https://doi.org/10.1111/jcmm.70580","url":null,"abstract":"<p>Acute kidney injury (AKI) is a complex disease caused by different causes, especially ischaemia–reperfusion (I/R) injury. Ferroptosis is the main form of I/R-induced organ injury, and blocking ferroptosis has demonstrated therapeutic potential in ameliorating organ injury. We investigated the roles of apoptosis-stimulating protein of p53 (iASPP) and hypoxia-inducible factor-1α (HIF-1α) in ferroptosis during renal I/R injury. HIF-1α gene was knocked out in a hypoxia/reoxygenation model of renal tubular epithelial cells, and iASPP overexpression and knockdown plasmids were transfected. In I/R mouse models, conditional knockout of HIF-1α mice and injection of overexpressed iASPP adeno-associated viruses were used to validate downstream ferroptosis-related changes. The results showed that the ferroptosis level of mice in the I/R group was increased, and the addition of Ferrostatin-1 (Fer-1) and FG-4592 could alleviate the ferroptosis. HIF-1α conditional knockout mice showed exacerbated ferroptosis. HIF-1α can directly interact with SLC7A11, a key ferroptosis regulator, modulating ferroptosis progression. Similar to HIF-1α, iASPP expression was significantly increased in the I/R group, and overexpression of iASPP upregulated HIF-1α and SLC7A11 expression, consequently mitigating ferroptosis-mediated damage. In summary, our study suggests that iASPP exerts renal protection during I/R injury by regulating the HIF-1α/SLC7A11 axis to suppress ferroptosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244723","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}