Experimental cell research最新文献

{"title":"Insulin-like growth factor-1 enhances β-amyloid protein clearance in HMC3 microglia via low-density lipoprotein receptor-related protein 1-mediated pathway","authors":"Hongsong Guo,&nbsp;Xiaoqian Peng,&nbsp;Xiao Zhang,&nbsp;John Bosco Ruganzu,&nbsp;Xiangyuan Wu,&nbsp;Mingtao Zhao,&nbsp;Pengbo Yang,&nbsp;Shengfeng Ji,&nbsp;Weina Yang","doi":"10.1016/j.yexcr.2026.114920","DOIUrl":"10.1016/j.yexcr.2026.114920","url":null,"abstract":"<div><div>β-amyloid protein (Aβ) deposition occurs years before cognitive symptoms appear and is considered one of the main causes underlying the pathogenic events that occur in Alzheimer's disease (AD). Mounting evidence suggests that the imbalance of Aβ production and clearance leads to the accumulation of Aβ and the subsequent formation of toxic Aβ aggregates. Aβ is internalized by microglia and transported to lysosomes for degradation, which is one of the main ways by which Aβ may be cleared from the brain. Insulin-like growth factor-1 (IGF-1) promotes clearance of Aβ in the brain by enhancing Aβ carrier proteins. Our previous study demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) mediates the internalization of Aβ_1-42 and lysosomal trafficking in primary cortical neurons. However, whether IGF-1 enhances the clearance of Aβ in microglia through the LRP1-mediated pathway and its underlying mechanisms is incompletely understood. Here, we reported that knockdown of LRP1 expression significantly decreased the internalization of Aβ_1-42 in HMC3 cells. Furthermore, pretreatment with IGF-1 significantly increased intracellular Aβ_1-42, indicating IGF-1 enhances HMC3 cells uptake of extracellular Aβ_1-42. Interestingly, the intracellular Aβ_1-42 in LRP1-knockdown HMC3 cells was reduced after preincubation with IGF-1. Thus, it was indicated that LRP1 is essential for IGF-1-enhanced internalization of Aβ_1-42 in HMC3 cells. Moreover, IGF-1 significantly inhibited the downregulation of PI3K, phospho-PI3K, Akt, and phospho-Akt induced by Aβ_1-42. Importantly, treatment with LY294002, a PI3K inhibitor, significantly reduced the intracellular Aβ_1-42 levels and decreased the expression of LRP1. These findings indicated that IGF-1 enhances the internalization of Aβ in a LRP1-dependent manner by activating the PI3K/Akt signaling pathway. Finally, we identified that IGF-1 promotes lysosomal proteolysis of Aβ_1-42 by increasing cathepsin B (CTSB) and cathepsin D (CTSD) expression. Consequently, these results demonstrated that IGF-1 promotes the internalization and lysosomal degradation of Aβ by microglia, which is an effective approach to lowering brain Aβ levels, and it might be a promising therapeutic target for AD.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 1","pages":"Article 114920"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AHNAK inhibits osteoporosis progression by stabilizing Smad1 protein","authors":"Weifei Zhang ,&nbsp;Hua Chen ,&nbsp;Tiantian Qi ,&nbsp;Dengbo Yao ,&nbsp;Hang Liu ,&nbsp;Hui Zeng ,&nbsp;Fei Yu ,&nbsp;Wenyu Zhou","doi":"10.1016/j.yexcr.2026.114899","DOIUrl":"10.1016/j.yexcr.2026.114899","url":null,"abstract":"<div><div>AHNAK is a structural scaffold protein implicated in a wide array of physiological functions. AHNAK mutations are highly prevalent in patients with osteoporosis, However, it is currently unknown whether AHNAK affects the progression of osteoporosis and the specific mechanism behind this effect. This study detected decreased AHNAK (AHNAK1) expression in bone tissues and bone marrow mesenchymal stem cells (BMSCs) of osteoporotic mice. Genetic knockdown of AHNAK inhibited osteogenic differentiation of BMSCs. Mechanistic investigations indicated that AHNAK functions through stabilizing Smad1 protein levels. Overexpression of Smad1 in AHNAK-knockdown BMSCs restored their osteogenic differentiation capacity. Furthermore, in vivo mouse experiments further confirmed these findings. Collectively, these findings indicate that AHNAK inhibits the progression of osteoporosis by stabilizing Smad1 protein.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114899"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Runx2 switch: unlocking osteoblast-related disorders through signaling pathways and non-coding RNAs","authors":"Somayeh Aslani ,&nbsp;Ashkan Kalantary-Charvadeh ,&nbsp;Roghayeh Abbasalipourkabir ,&nbsp;Nasrin Ziamajidi","doi":"10.1016/j.yexcr.2026.114921","DOIUrl":"10.1016/j.yexcr.2026.114921","url":null,"abstract":"<div><div>Osteoblasts, specialized bone-forming cells, differentiate from mesenchymal stem cells (MSCs). In recent years, stem cell-derived osteoblasts have emerged as potential choices for the treatment of bone-related disorders. A complex network of regulatory elements, including signaling pathways, transcription factors, and non-coding RNAs (ncRNAs), orchestrates MSCs differentiation. Among the key regulators of osteoblast differentiation is Runt-related transcription factor 2 (Runx2), a master transcription factor essential for osteogenic commitment. Elucidating the molecular mechanisms that regulate Runx2 expression and function is critical for the treatment of osteoblast-related disease. Runx2 is regulated through signaling pathways and a complex, post-transcriptional competing endogenous RNA (ceRNA) network. In this network, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) sequester microRNAs (miRNAs), thereby fine-tuning Runx2 expression. Signaling pathways can also indirectly regulate Runx2 by inducing the expression of osteo-regulatory miRNAs. This review highlights the regulatory role of Runx2 during osteoblastic differentiation. It also explores how signaling pathways, lncRNAs, circRNAs, and other factors interact with Runx2-regulatory miRNAs involved in this process.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114921"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KAT5/8-mediated GPX4 lactylation facilitates ferroptosis and inflammation in diabetic retinopathy","authors":"Yan Zhou,&nbsp;Min Du","doi":"10.1016/j.yexcr.2026.114915","DOIUrl":"10.1016/j.yexcr.2026.114915","url":null,"abstract":"<div><div>Diabetes-induced hyperglycemia promotes retinal capillary endothelial cell dysfunction, contributing to diabetic retinopathy. In this study, we reveal that high glucose (HG) drives ferroptosis and inflammation through lactate-mediated GPX4 lactylation. HG conditions enhance glycolysis and lactate production, leading to increased lactylation of GPX4, a process mediated by the acetyltransferases KAT5 and KAT8. GPX4 lactylation reduces its antioxidant function, promoting lipid peroxidation, ferroptosis, and inflammation. Specifically, HG exposure significantly increases malondialdehyde (MDA) levels, decreases GSH levels, and elevates lipid ROS, while simultaneously inducing pro-inflammatory cytokine expression (<em>IL6</em>, <em>TNF</em>, and <em>IL1B</em>). Inhibition of KAT5 and KAT8 markedly reduces GPX4 lactylation, restores redox balance, suppresses ferroptosis, and mitigates inflammation. Collectively, our findings identify KAT5- and KAT8-mediated GPX4 lactylation as a key mechanism underlying HG-induced ferroptosis and inflammation in diabetic retinopathy, highlighting its potential as a promising therapeutic target.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114915"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDC6 promotes keratinocyte senescence through the CCND1/P53 signaling in ischemia-reperfusion injury-induced pressure injury","authors":"Chenming Wang ,&nbsp;Shanshan Zhu ,&nbsp;Meige Dai ,&nbsp;Hui Chen","doi":"10.1016/j.yexcr.2026.114903","DOIUrl":"10.1016/j.yexcr.2026.114903","url":null,"abstract":"<div><div>Pressure injuries develop when prolonged compression of the skin and subcutaneous tissue impairs blood circulation, leading to localized tissue ischemia, degeneration, and ultimately necrosis. Ischemia-reperfusion(I/R) injury is one of the key pathological mechanisms underlying pressure injury formation. While cellular senescence has been implicated in I/R-related pathologies, its role in pressure injury development remains unclear. We aimed to elucidate the mechanisms of keratinocyte senescence in cutaneous I/R injury. An in vitro hypoxia/reoxygenation (H/R) model was employed to simulate I/R injury using human immortalized keratinocytes (HaCaT). H/R induction significantly exacerbated the senescence response, as characterized by reduced cell proliferation, increased apoptosis, elevated SA-β-galactosidase (SA-β-gal) activity, and upregulated expression of senescence markers (p16 and p21). Quantitative proteomic analysis identified CDC6 as a prominently upregulated protein under H/R conditions. siRNA-mediated CDC6 knockdown attenuated keratinocyte senescence, restored G1/S phase cyclin-D1 (CCND1) expression, and suppressed p53 levels, demonstrating its regulatory role in senescence via the p53/CCND1 pathway. Furthermore, protein interaction network analysis and experimental validation revealed CDC6's direct binding with origin recognition complex 2 (ORC2), evidenced by nuclear colocalization (immunofluorescence) and physical interaction (co-immunoprecipitation). Collectively, our findings pioneers the mechanistic elucidation of CDC6 in pressure injury pathology, proposing senescence-targeted interventions as a novel therapeutic strategy for ulcer management.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114903"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “A human tissue-based model of renal inflammation” [Exp. Cell Res. 2024 Nov 1;443(1):114309]","authors":"Camilla Merrild ,&nbsp;Gitte A. Pedersen ,&nbsp;Kristian W. Antonsen ,&nbsp;Mia G. Madsen ,&nbsp;Anna K. Keller ,&nbsp;Holger J. Møller ,&nbsp;Lene N. Nejsum ,&nbsp;Henricus A.M. Mutsaers ,&nbsp;Rikke Nørregaard","doi":"10.1016/j.yexcr.2026.114896","DOIUrl":"10.1016/j.yexcr.2026.114896","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114896"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of biliverdin reductase A leads to ROS-independent sensitization of ovarian adenocarcinoma cells to gemcitabine","authors":"Zuzana Solárová ,&nbsp;Kristína Danková ,&nbsp;Pavol Harvanik ,&nbsp;Peter Bober ,&nbsp;Petra Majerová ,&nbsp;Radka Michalková ,&nbsp;Mangesh Bhide ,&nbsp;Peter Solár","doi":"10.1016/j.yexcr.2026.114905","DOIUrl":"10.1016/j.yexcr.2026.114905","url":null,"abstract":"<div><h3>Aims</h3><div>Biliverdin reductase A (BLVRA) is a key enzyme in bilirubin metabolism, where it reduces biliverdin to bilirubin. Bilirubin is a potent antioxidant that protects cells from oxidative stress. Therefore, reduced or deregulated BLVRA activity may contribute to increased oxidative DNA damage, which is one of the factors leading to the neoplastic transformation of cells.</div></div><div><h3>Methods</h3><div>Human ovarian adenocarcinoma A2780 cells were transfected with a PiggyBac vector to achieve BLVRA overexpression. A2780 clones showing the most significant BLVRA gene overexpression were analyzed by proteomics and flow cytometry to assess rective oxygen species (ROS) production.</div></div><div><h3>Results</h3><div>Our results indicate that BLVRA overexpression increases the sensitivity of A2780 cells to doxorubicin and gemcitabine, with the most pronounced effect observed in the J clone. In this clone, the highest level of BLVRA overexpression correlated with significant alterations in the p53 signaling pathway. Upregulation of key effectors such as Bax and CDKN2A indicates a potential role for BLVRA in promoting pro-apoptotic responses. Moreover, <em>BLVRA</em> overexpression increased the sensitivity of A2780 cells to gemcitabine independently of ROS.</div></div><div><h3>Conclusions</h3><div>This study broadens our understanding of BLVRA in ovarian cancer. In cells with intact p53 signaling, BLVRA overexpression can paradoxically enhance cytotoxic response to certain drugs, particularly gemcitabine.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114905"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of Gfi1 induced by LSD1 inhibitor protects against cisplatin-induced ototoxicity through attenuating pyroptosis","authors":"Zihe Zhao ,&nbsp;Jingjing Luo ,&nbsp;Dengbin Ma ,&nbsp;Siyu Li ,&nbsp;Shaoqin Cen ,&nbsp;Hanqi Fan ,&nbsp;Zhenxing Hou ,&nbsp;Junze Lu ,&nbsp;Cheng Cheng ,&nbsp;Xiaoyun Qian ,&nbsp;Xia Gao ,&nbsp;Ao Li","doi":"10.1016/j.yexcr.2026.114902","DOIUrl":"10.1016/j.yexcr.2026.114902","url":null,"abstract":"<div><div>Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity. Identifying potential therapeutic targets to mitigate cisplatin-induced hearing loss has become a crucial goal. In this study, we demonstrated that the LSD1 inhibitor S2101 could protect against cisplatin-induced ototoxicity (CIO) by upregulating Gfi1 expression. Mechanistically, we investigated the regulatory relationship between Gfi1 and Trim27. Our findings indicated that Gfi1 could bind to the Trim27 promoter region, activating its transcription. The subsequent upregulation of Trim27 significantly attenuated hair cell pyroptosis, highlighting the therapeutic potential of the Gfi1-Trim27 pathway. These results collectively underscore the critical function of Gfi1 in protecting against cisplatin-induced hearing loss and provide novel insights into potential therapeutic strategies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 2","pages":"Article 114902"},"PeriodicalIF":3.5,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of EphA2 by Src counteracts Src-induced loss of cell adhesion","authors":"Misuzu Takada ,&nbsp;Mayu Murata ,&nbsp;Shuhei Soeda ,&nbsp;Takuya Honda ,&nbsp;Ryuzaburo Yuki ,&nbsp;Yuji Nakayama","doi":"10.1016/j.yexcr.2026.114898","DOIUrl":"10.1016/j.yexcr.2026.114898","url":null,"abstract":"<div><div>The receptor tyrosine kinase EphA2 is highly expressed in various cancers, and its elevated levels are associated with poor prognosis. Although Src has been shown to increase EphA2 expression partly through ERK signaling, the functional consequences of EphA2 upregulation remain unclear. In this study, we investigated the role of EphA2 upregulation by active Src in cell adhesion. We utilized HeLa S3-derived HeLa S3/v-Src cells, which allow inducible v-Src expression upon doxycycline (Dox) treatment. Dox treatment induced v-Src expression, cell rounding, and a marked increase in global tyrosine phosphorylation. Consistent with previously reports, EphA2 expression was upregulated following v-Src induction. Time-course analysis revealed that EphA2 knockdown accelerated v-Src-induced cell rounding. Similarly, c-Src also upregulated EphA2 and induced cell rounding. Paxillin staining demonstrated that c-Src expression increased both the number and area of focal adhesions, as well as paxillin intensity at these sites. All of these effects were abolished by EphA2 knockdown. In conclusion, Src activity upregulates EphA2 expression, and increased EphA2 counteracts Src-induced cell detachment. However, as Src signaling intensifies, it overrides the counteracting effect of EphA2, resulting in cell rounding and detachment. The balance between Src and EphA2 may act as a key regulator of cellular adhesion dynamics.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 1","pages":"Article 114898"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP18 promotes cell proliferation and inhibits ferroptosis by stabilizing HDAC3 in endometrial carcinoma","authors":"Fang Tong ,&nbsp;Xue Gao ,&nbsp;Yuhong Shang","doi":"10.1016/j.yexcr.2026.114900","DOIUrl":"10.1016/j.yexcr.2026.114900","url":null,"abstract":"<div><div>Endometrial cancer (EC) represents one of the most prevalent malignancies of the female reproductive system. Ferroptosis, a recently identified form of programmed cell death, has garnered increasing attention in cancer research. Ubiquitin-specific peptidase 18 (USP18), a member of the deubiquitinating enzyme family, has been recognized as an oncoprotein in various cancers; however, its functional role and underlying mechanisms in EC remain largely unexplored. In this study, we found that USP18 was markedly upregulated in EC patients (n = 15, stage I; n = 4, stage II and n = 1, stage III), and elevated USP18 expression correlated with unfavorable prognosis. Functional assays demonstrated that knockdown of USP18 significantly inhibited EC cell proliferation. Moreover, USP18 silencing promoted the accumulation of lipid reactive oxygen species (ROS), malondialdehyde (MDA), and Fe²⁺, thereby enhancing erastin-induced ferroptosis. In contrast, USP18 overexpression produced opposing effects. These in vitro findings were further validated <em>in vivo</em>, where USP18 knockdown suppressed tumor growth and promoted ferroptosis. Mechanistic investigations revealed that USP18 interacted with and deubiquitinated histone deacetylase 3 (HDAC3), thus leading to its stabilization. Subsequent rescue experiments confirmed that the tumor-promoting effects of USP18 were abrogated upon HDAC3 knockdown. Taken together, our results identify the USP18/HDAC3 axis as a key regulator of EC cell proliferation and ferroptosis suppression, underscoring the potential of USP18 as a therapeutic target in EC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"456 1","pages":"Article 114900"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}