Experimental cell research最新文献

{"title":"Overcoming multidrug resistance in cancer cells targeting ABC transporter ABCB1 with tyrosine kinase inhibitor: Olverembatinib","authors":"Bohan Zhang ,&nbsp;Xiang Chen ,&nbsp;Xingduo Dong ,&nbsp;Yidong Li ,&nbsp;Letao Bo ,&nbsp;Harsh Patel ,&nbsp;Brian Chou ,&nbsp;Shanzhi Wang ,&nbsp;Zhe-Sheng Chen","doi":"10.1016/j.yexcr.2025.114851","DOIUrl":"10.1016/j.yexcr.2025.114851","url":null,"abstract":"<div><div>The overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) remains a primary challenge in overcoming multidrug resistance (MDR) in cancer cells. This study investigates the potential of olverembatinib, a third-generation tyrosine kinase inhibitor (TKI), to reverse ABCB1-mediated MDR and enhance the efficacy of chemotherapeutic drugs. Non-cytotoxic concentrations of olverembatinib significantly increased the sensitivity of ABCB1-overexpressing cells to paclitaxel and vincristine. Mechanistic analyses revealed that olverembatinib did not alter the expression or localization of ABCB1 but inhibited its drug efflux function, resulting in increased intracellular drug retention. Additionally, olverembatinib activated the ATPase activity of ABCB1 in a concentration-dependent manner and exhibited potent binding affinity to ABCB1 in docking simulations. These findings suggest that olverembatinib holds promise as a potent reversal agent for MDR, paving the way for its integration into novel combination chemotherapy regimens to improve cancer treatment outcomes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"455 1","pages":"Article 114851"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736288","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":"MicroRNA-mediated metabolic control in HCC: From molecular networks to therapy","authors":"Dhuha D.M. Alrawi ,&nbsp;Shahd rajab farhan ,&nbsp;Ali G. Alkhathami ,&nbsp;Chou-Yi Hsu ,&nbsp;Zahraa Khudhair Abbas Al-Khafaji ,&nbsp;Amr Ali Mohamed Abdelgawwad El-Sehrawy ,&nbsp;Yasser Fakri Mustafa ,&nbsp;Wael Nabil ,&nbsp;Zuhair I. Al-Mashhadani","doi":"10.1016/j.yexcr.2025.114853","DOIUrl":"10.1016/j.yexcr.2025.114853","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common histological subtype of primary liver cancer, accounting for nearly 80–90 % of all liver cancer cases. While ‘liver cancer’ refers broadly to all malignant tumors arising in the liver (including HCC, cholangiocarcinoma, and others), HCC specifically originates from hepatocytes. HCC is characterized by extensive metabolic reprogramming, including not only higher levels of aerobic glycolysis, de novo lipogenesis, and altered glutamine metabolism but also altered one-carbon metabolism. Enhanced metabolic adaptation markers, therefore, serve as key indicators of malignant transformation but also contribute to cancer progression by promoting cell proliferation, metastasis, immune modulation, and therapy evasion. Emerging evidence suggests microRNAs (miRNAs) can coordinate these metabolic adaptations by targeting key enzymes, transporters, transcription factors, signaling molecules, or pathways involved in metabolism. For instance, miR-122, miR-27a, miR-148a, and miR-4310 inhibit lipid accumulation and mitochondrial dysfunction, while miR-21, miR-103a, and miR-30b-5p promote glycolysis, lipogenesis, and anabolic metabolism. Long non-coding RNAs (lncRNAs) and exosomal miRNAs interact with these upstream regulators to form a heterogeneous network of non-coding RNAs. These networks participate in remodeling the tumor microenvironment, modulating the immune response, and facilitating metabolic adaptation in HCC. miRNAs are ideal for the potential stratification of HCC risk, prognosis, and therapeutic response, as they occupy key upstream positions in regulatory hierarchies and have been described as both biomarkers and potential metabolic switches. This study aims to elucidate the role of microRNAs in regulating metabolic pathways in HCC by delineating numerous miRNA-target interactions involved in glycolysis, lipid, amino acid, and nucleotide metabolism. This knowledge will enable us to identify novel diagnostic biomarkers and therapeutic targets for prognosis and to explore effective novel precision treatment strategies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114853"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686878","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":"Glycolysis inhibition and AMPK activation: a critical role of CTRP1 deficiency in the treatment of hypoxia-induced pulmonary hypertension","authors":"Yu Zhang ,&nbsp;Weiqiang Chen ,&nbsp;Kai Yang,&nbsp;Tao Hao,&nbsp;Wenfeng Cao,&nbsp;Shuqiang Dong","doi":"10.1016/j.yexcr.2025.114838","DOIUrl":"10.1016/j.yexcr.2025.114838","url":null,"abstract":"<div><div>In pulmonary hypertension (PH), metabolic enhancement of glycolysis drives a hyperproliferative and apoptosis-resistant phenotype in pulmonary artery smooth muscle cells (PASMCs), which is a key pathological process leading to pulmonary vascular remodeling. We aimed to uncover the role of CTRP1, a gene responsible for regulating glycolysis, in the modulation of PH-related pathogenesis. In the PH mouse and cell models established by hypoxia stimulation, the regulatory mechanism of CTRP1 deletion on the pathological characteristics of PH was explored. CTRP1 levels were significantly upregulated in PH mice, accompanied by an abnormal increase in lactate production and glycolysis-related key protein expressions (HK2 and PDHK1). Inhibition of CTRP1 markedly improved pulmonary artery pressure and right ventricular function in PH mice by reducing glycolysis levels. In vitro experiments further observed that CTRP1 knockdown suppressed the hypoxia-induced hyperproliferation and anti-apoptosis phenotype of PASMCs, with inhibition of glycolysis. Mechanically, downregulated CTRP1 resulted in p-AMPK activation and p-AKT/mTOR inhibition. This beneficial effect was reversed by AMPKα2 deficiency. Overall, CTRP1 deficiency reverses the hypoxia-induced hyperproliferation and antiapoptotic capacity of PASMCs by weakening glycolysis. These results provide evidence for CTRP1 as a potential therapeutic target in PH.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114838"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596346","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":"miR-98-3p/VEGFA axis mediates MALAT1-induced angiogenesis in ovarian tumors","authors":"Mengxin Zhang ,&nbsp;Yu Zhang ,&nbsp;Jiabao Xu,&nbsp;Wei Li,&nbsp;Mengjiao Hu,&nbsp;Wenhong Liu,&nbsp;Ye Xu,&nbsp;Fangfang Tao","doi":"10.1016/j.yexcr.2025.114844","DOIUrl":"10.1016/j.yexcr.2025.114844","url":null,"abstract":"<div><div>The functional role of MicroRNA miR-98-3p in ovarian cancer is largely unexplored and its molecular mechanisms remain incompletely understood. In this study, we identified a novel regulatory axis involving MALAT1, miR-98-3p, and VEGFA in ovarian cancer angiogenesis. The study focuses on ovarian cancer-related proliferation and migration effects, primarily involving the angiogenesis effects of ovarian cancer. RNA sequencing following MALAT1 knockdown in HEY-T30 cells revealed significant alterations in several miRNAs, particularly miR-98-3p. Luciferase reporter assays confirmed direct binding between MALAT1 and miR-98-3p, establishing MALAT1 as a competing endogenous RNA (ceRNA) for miR-98-3p. Bioinformatic analysis and luciferase reporter assays further identified VEGFA as a direct target of miR-98-3p. Clinical database analysis demonstrated a positive correlation between MALAT1 and VEGFA expression, with elevated levels of both being significantly associated with poor overall survival in ovarian cancer patients. Functionally, both MALAT1 knockdown and miR-98-3p overexpression significantly impaired HUVEC tube formation, proliferation, and migration, which could be reversed by miR-98-3p inhibition. In vivo, miR-98-3p overexpression in subcutaneous xenografts resulted in reduced tumor volume, weight, vasculature, and blood perfusion, along with decreased expression of VEGFA, MMP2, and MMP9. These findings elucidate a MALAT1/miR-98-3p/VEGFA regulatory axis that modulates tumor angiogenesis in ovarian cancer, providing potential therapeutic targets for this malignancy.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114844"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676838","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":"Ferroptosis modulates invasion and migration in prostate cancer PC-3M subclones","authors":"Yuliang Rao ,&nbsp;Siyu Liu ,&nbsp;Aicui Ma ,&nbsp;Li Xu ,&nbsp;Jun Guo ,&nbsp;Zuyue Sun","doi":"10.1016/j.yexcr.2025.114847","DOIUrl":"10.1016/j.yexcr.2025.114847","url":null,"abstract":"<div><div>Prostate cancer (PCa) metastasis remains a formidable clinical challenge, underscoring the urgent need to uncover its underlying molecular mechanisms. Leveraging the PC-3M cell line and its sublines with divergent metastatic potentials (PC-3M-1E8, highly metastatic; PC-3M-2B4, low-metastatic), this study investigated the role of ferroptosis, a form of iron-dependent regulated cell death, in PCa metastasis. Functional assays demonstrated that PC-3M-1E8 cells exhibited significantly enhanced proliferation, migration, invasion, and clonogenic capacity compared to PC-3M-2B4 cells. Proteomic analysis identified 5502 differentially expressed proteins, with GSEA pinpointing ferroptosis as the most significantly enriched pathway (NES = 2.8, FDR <em>&lt;</em> 0.001) in PC-3M-1E8 cells. Key ferroptosis regulators, including GPX4 (1.4-fold), GCLM (1.6-fold), GCLC (1.5-fold), and TFRC (1.8-fold), were upregulated in PC-3M-1E8, while ACSL4 (0.7-fold) and VDAC3 (0.6-fold) were downregulated, constructing a ferroptosis-resistant network. Functional validation revealed that PC-3M-1E8 cells were more resistant to ferroptosis induction, evidenced by 3.68-fold higher GPX4 expression, 1.37-fold elevated GSH/GSSG ratios, and blunted iron responses. These findings establish an inverse correlation between ferroptosis sensitivity and PCa metastatic potential, providing a novel perspective on PCa metastasis by linking iron metabolism reprogramming to metastatic competence. Clinically, the identified ferroptosis-related signatures offer potential as predictive biomarkers for metastatic risk, and ferroptosis induction emerges as a promising therapeutic strategy for metastatic PCa. Future research should focus on exploring the crosstalk between ferroptosis and other cancer-related pathways to develop more effective targeted therapies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114847"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654073","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":"lincRNA-p21 drives apoptosis and calcification of vascular smooth muscle cell via small extracellular vesicles under hyperphosphatemic conditions in chronic kidney disease","authors":"Jianbing Hao,&nbsp;Siyu Wang,&nbsp;Lirong Hao","doi":"10.1016/j.yexcr.2025.114779","DOIUrl":"10.1016/j.yexcr.2025.114779","url":null,"abstract":"<div><div>Vascular calcification, a major contributor to cardiovascular morbidity, involves pathological osteogenic transdifferentiation of vascular smooth muscle cell (VSMC) under hyperphosphatemic conditions in chronic kidney disease. This study investigates the role of lincRNA-p21 and small extracellular vesicles in phosphate-induced mouse aortic smooth muscle cell (MASMC) calcification. Exposure to phosphate (2.6 mmol/L) triggered time-dependent calcification, characterized by enhanced calcium deposition, endoplasmic reticulum remodeling, and intracellular calcium accumulation (p &lt; 0.05 vs. 24/48-h controls). Concurrently, the expression of osteogenic markers (BGP, OCN, and OPN) and lincRNA-p21 was significantly upregulated, whereas the expression of contractile phenotype-specific markers (SM22α, SM-MHC, and SM α-actin) was markedly down-regulated. This pattern of gene expression was correlated with MASMC osteogenic transdifferentiation. Small extracellular vesicles isolated from phosphate-treated MASMC exhibited elevated lincRNA-p21 levels (p &lt; 0.05) and induced calcification and apoptosis in recipient cells, suggesting small extracellular vesicles-mediated propagation of calcific signals. Functional studies demonstrated that lincRNA-p21 overexpression exacerbated calcification, apoptosis, and osteogenic marker expression, while its knockdown attenuated these effects (p &lt; 0.05). Time-course analyses revealed lincRNA-p21 dynamically regulates small extracellular vesicles secretion, calcium accumulation, and apoptotic pathways, acting as a molecular switch driving phosphate-induced calcification. These findings establish lincRNA-p21 as a critical mediator of MASMC calcification via small extracellular vesicles-dependent mechanisms, offering insights into therapeutic strategies for vascular calcification.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114779"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530515","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":"Fbxo45 promotes cell viability, invasion and sunitinib resistance of clear cell renal cell carcinoma by targeting Erbin","authors":"Xueshan Pan ,&nbsp;Ke Yu ,&nbsp;Kai Chen ,&nbsp;Jiao Wang ,&nbsp;Zheng Huang ,&nbsp;Jiewen Wang ,&nbsp;Tong Cao ,&nbsp;Jia Ma","doi":"10.1016/j.yexcr.2025.114839","DOIUrl":"10.1016/j.yexcr.2025.114839","url":null,"abstract":"<div><div>The mechanisms underlying the development and progression of clear cell renal cell carcinoma (ccRCC) and its sunitinib resistance are elusive. Fbxo45 is a member of the F-box protein family that has been demonstrated to participate in tumorigenesis. However, the role of Fbxo45 in ccRCC progression has not been characterized. This study aims to investigate the biological functions and molecular mechanism of Fbxo45 in ccRCC progression. We found that Fbxo45 knockdown inhibited the viability and motility of ccRCC cells, while Fbxo45 overexpression resulted in the opposite phenotype. Ectopic expression of Fbxo45 promoted tumor growth in mice. Fbxo45 expression was negatively correlated with Erbin expression, which has been reported to mediate anti-tumor activities in ccRCC. Furthermore, Fbxo45 facilitated ccRCC cell viability and motility by inhibiting Erbin. Notably, Fbxo45 upregulation reduced sunitinib sensitivity in ccRCC cells. Our results suggest that Fbxo45 could be a potential target for ccRCC treatment and sunitinib resistance.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114839"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596335","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":"Sagittaria sagittifolia polysaccharide regulates Nrf2-mediated antioxidant to improve apoptosis and ferroptosis in high glucose-induced lens epithelial cells","authors":"Man-yu Zhou ,&nbsp;Yang Jiang ,&nbsp;Jia-zhen Ding ,&nbsp;Yao Liang ,&nbsp;Jian-bin Sun ,&nbsp;Bing-qing Liu ,&nbsp;Yan Liao","doi":"10.1016/j.yexcr.2025.114841","DOIUrl":"10.1016/j.yexcr.2025.114841","url":null,"abstract":"<div><div>Diabetic cataract (DC), a primary ocular complication of diabetes mellitus, remains a leading cause of global blindness. The bioactive polysaccharide <em>Sagittaria sagittifolia</em> polysaccharide (SSP) exhibits remarkable antioxidant and anti-apoptotic efficacy in age-related cataract models, yet its DC therapeutic potential is unexplored. This study investigated SSP's protective effects against high glucose (HG)-induced damage across three experimental models, focusing on nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant in apoptosis and ferroptosis regulation. In ex vivo rat lenses, SSP pretreatment (1 mg/mL, 24 h) significantly attenuated HG-induced (25 mM, 48 h) lens opacification. In human lens epithelial B3 (HLEB3) cells, SSP pretreatment (1 mg/mL, 24 h) markedly improved cell viability and proliferation under HG conditions (150 mM, 72 h). Mechanistically, SSP significantly decreased oxidative stress markers (malondialdehyde, protein carbonyls, reactive oxygen species) while restoring mitochondrial function and enhancing antioxidant capacity (glutathione levels, catalase activity). SSP activated the Nrf2 pathway, regulating key antioxidant proteins (NAD(P)H quinone dehydrogenase 1, heme oxygenase-1, thioredoxin (Trx), Trx2 and glutaredoxin 1 to mitigate HG-induced oxidative damage. SSP exerted anti-apoptotic effects by upregulating B-cell lymphoma-2 (Bcl-2) while suppressing Bcl-2-associated X and cleaved caspase-3 expression. SSP modulated ferroptosis by increasing Ferritin, system Xc⁻, and glutathione peroxidase 4 (GPX4) while reducing Fe²⁺ and acyl-CoA synthetase long-chain family member 4 (ACSL4) levels. In STZ-induced diabetic mice, SSP treatment ameliorated lens epithelial cells (LECs) morphological damage and reduced protein expression of caspase-3 and ACSL4, whereas increased protein expression of GPX4 and ferritin. Crucially, upon Nrf2 knockdown in HLEB3 cells via short interfering RNA, SSP confirmed its protective role by activating Nrf2 to inhibite apoptosis and ferroptosis. Collectively, these findings demonstrate that SSP protects LECs against HG-induced damage through Nrf2-mediated coordination of antioxidant defense, anti-apoptotic, and anti-ferroptotic mechanisms, highlighting its therapeutic potential for DC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114841"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616578","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":"Elucidating the impact of trans-ned-19 on two-Pore channel 2 mutants of Dictyostelium: changes in intracellular calcium levels and subsequent effect on autophagic flux","authors":"Ashima Thakur,&nbsp;Shweta Saran","doi":"10.1016/j.yexcr.2025.114829","DOIUrl":"10.1016/j.yexcr.2025.114829","url":null,"abstract":"<div><div>Two-Pore Channel 2 (TPC2) are calcium (Ca²⁺) release channels regulated by Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP), primarily localized to the endolysosomal system. TPC2 regulates diverse Ca²⁺-dependent processes such as cell proliferation, development, migration, and autophagy. In the protist <em>Dictyostelium discoideum</em>, intracellular Ca²⁺ levels and autophagy are key determinants of cell-fate, particularly for stalk cell differentiation. To investigate the involvement of <em>Dd</em>TPC2 in NAADP-mediated Ca²⁺ signalling, we treated wild-type (Ax2) and various <em>tpc2</em> mutant strains, like overexpressors (<em>tpc2</em>^<em>OE</em>), knockout (<em>tpc2</em>^-), and rescue (<em>tpc2</em>^<em>Res</em>), with both NAADP-AM (NAADP agonist) and trans-Ned-19 (NAADP antagonist). Our findings show that trans-Ned-19 does not specifically inhibit <em>Dd</em>TPC2 activity during the proliferative (vegetative) stage, but acts as a specific TPC2 inhibitor in freshly starved cells or during multicellular development, as the phenotypes displayed by trans-Ned-19 treated Ax2 cells were similar to <em>tpc2</em>^<em>-</em> cells. Trans-Ned-19 colocalizes with lysosomes, consistent with the subcellular distribution of TPC2. Fluid-phase endocytosis was reduced in <em>tpc2</em>^- cells, implicating TPC2 in endolysosomal function. Intracellular calcium measurements demonstrated that NAADP regulates Ca²⁺ signalling through TPC2, as both NAADP-AM and trans-Ned-19 significantly modulated intracellular free Ca²⁺ levels in TPC2-expressing strains. Notably, trans-Ned-19 treatment reduced autophagic flux in Ax2 cells to <em>tpc2</em>^<em>-</em> levels, demonstrating a positive correlation between TPC2 and autophagic flux, further supported by rapamycin and 3-methyladenine treatment results. This study highlights TPC2 as a pivotal regulator of NAADP-mediated Ca²⁺ signalling and autophagy in <em>Dictyostelium</em>, with broad implications for understanding these processes in higher eukaryotes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114829"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581909","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":"Augmenter of liver regeneration alleviates lipid accumulation in MASLD through ATF3-CD36 axis","authors":"Weichun Xiao ,&nbsp;Yuan Wu ,&nbsp;Ling Qin ,&nbsp;Jing Zhang ,&nbsp;Wei An","doi":"10.1016/j.yexcr.2025.114823","DOIUrl":"10.1016/j.yexcr.2025.114823","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive lipid deposition in hepatocytes. Augmenter of liver regeneration (ALR, encoded by the <em>Gfer</em> gene), a survival factor in liver cells, protects the liver against various injuries, whereas downregulation of ALR expression accelerates MASLD progression in mice. CD36 functions as a long chain free fatty acid transporter, playing a crucial role during pathogenesis of MASLD. Herein, the expression level of CD36 was found to significantly decrease in ALR-transfected (ALR-Tx) HepG2 cells and upregulated in shRNA-ALR (shALR) cells after oleic acid/palmitic acid treatment. Furthermore, CD36 expression was markedly elevated in MASLD model mice with heterozygous <em>Gfer</em> knockdown (Gfer^+/−) fed a high-fat diet,as well as model mice with liver-specific <em>Gfer</em> knockout (Gfer-CKO). Lipid uptake increased and lipophagy was suppressed in shALR HepG2 cells, and conversly, lipid uptake reduced and lipophagy was promoted in ALR-Tx HepG2 cells. After downregulation of CD36 expression by siRNA-CD36 in shALR cells, lipid accumulation markedly decreased, and lipophagy was stimulated. Further, the mRNA and protein expression of ATF3 (Activating Transcription Factor 3) were found to substantially elevated and decreased in ALR-Tx cells and shALR cells respectively, and CD36 expression was induced after ATF3 was knock down. Our results thus suggest that lack of ALR aggravates lipid deposition in MASLD partly through the ATF3-CD36 axis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114823"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530556","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}