Journal of Molecular Cell Biology最新文献

ITIH5 Drives Adipocyte Differentiation and Obesity-Associated Metabolic Dysregulation via PI3K/AKT Signaling Activation. ih5通过PI3K/AKT信号激活驱动脂肪细胞分化和肥胖相关代谢失调

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-05-08 DOI: 10.1093/jmcb/mjag016

Dan Li, Maoxiang Xu, Jie Li, Mengliu Yang, Gangyi Yang, Ling Li

{"title":"ITIH5 Drives Adipocyte Differentiation and Obesity-Associated Metabolic Dysregulation via PI3K/AKT Signaling Activation.","authors":"Dan Li, Maoxiang Xu, Jie Li, Mengliu Yang, Gangyi Yang, Ling Li","doi":"10.1093/jmcb/mjag016","DOIUrl":"https://doi.org/10.1093/jmcb/mjag016","url":null,"abstract":"Obesity markedly increases the risk of type 2 diabetes, highlighting the urgent need for novel therapeutic targets. The inter-alpha-trypsin inhibitor heavy chain 5 (ITIH5), which is predominantly produced by the adipose tissue, has emerged as a potential regulatory factor in obesity; however, the specific underlying mechanisms remain unclear. In this study, we identified ITIH5 as a key factor upregulated in obesity and closely associated with adipocyte differentiation and metabolic regulation. ITIH5 expression was significantly elevated in the adipose tissue of obese mice. In vitro experiments revealed that ITIH5 knockdown suppressed 3T3-L1 adipocyte differentiation, lipid accumulation, and inflammatory cytokine secretion, whereas ITIH5 overexpression markedly enhanced these effects. Mechanistically, activation of the PI3K/AKT signaling pathway was found to mediate ITIH5-induced adipogenic differentiation and lipid synthesis. Consistent with these findings, in vivo knockdown of ITIH5 in the inguinal white adipose tissue alleviated high-fat diet-induced obesity, reduced adipocyte hypertrophy, improved glucose tolerance, and increased energy expenditure. Conversely, overexpression of ITIH5 aggravated metabolic dysfunction. Collectively, these findings indicate that ITIH5 promotes adipogenesis and obesity progression via the PI3K/AKT pathway, providing a potential therapeutic target for obesity intervention.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZBTB7B inhibits glioma tumorigenicity by upregulating GPR17 and CXCL10. ZBTB7B通过上调GPR17和CXCL10抑制胶质瘤的致瘤性。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-29 DOI: 10.1093/jmcb/mjaf043

Linmei Zhang, Haozhe Zhang, Chenxi Wang, Aoxin Jiang, Fei Zhao, Sifan Yang, Hong Lei, Xuelan Yu, Juan Ren, Chengfang Tang, Xiaofei Wang, Yanke Chen

{"title":"ZBTB7B inhibits glioma tumorigenicity by upregulating GPR17 and CXCL10.","authors":"Linmei Zhang, Haozhe Zhang, Chenxi Wang, Aoxin Jiang, Fei Zhao, Sifan Yang, Hong Lei, Xuelan Yu, Juan Ren, Chengfang Tang, Xiaofei Wang, Yanke Chen","doi":"10.1093/jmcb/mjaf043","DOIUrl":"10.1093/jmcb/mjaf043","url":null,"abstract":"The transcription factor ZBTB7B has been identified as a potential tumor suppressor through a CRISPR-Cas9-based functional screen of tumor-associated genes, as overexpression of ZBTB7B could significantly suppress tumor growth in the models of breast cancer brain metastasis, which prompted our further exploration of its inhibitory role in glioma. To elucidate the underlying mechanisms of this suppressive effect, lentiviral-mediated ZBTB7B overexpression was established in U118 and GL261 glioma cell lines, and systematic evaluation of tumorigenic capacity was performed through in vitro and xenograft assays. The results showed that ZBTB7B transcriptionally activated GPR17 expression, which suppressed protein kinase A phosphorylation, amplified mitochondrial reactive oxygen species generation, and triggered Caspase3-dependent apoptosis. Meanwhile, ZBTB7B upregulated CXCL10 secretion, which markedly enhanced CD4+ and CD8+ T cell accumulation. Clinical validation through multiplex immunofluorescence staining on a tissue microarray of 129 glioma samples revealed a progressive loss of ZBTB7B protein expression across WHO grades II to IV, inversely correlating with tumor malignancy. These findings demonstrate ZBTB7B as a dual-function tumor suppressor that concurrently induces intrinsic apoptosis and remodels the tumor immune microenvironment in glioma toward a 'hot' phenotype. Therefore, we propose ZBTB7B reactivation as a novel therapeutic strategy for glioma.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis. 神经毒物（MPTP和6-羟多巴胺）和α-突触核蛋白诱导帕金森病的致病机制：一个统一的假说。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-03 DOI: 10.1093/jmcb/mjaf041

Bao Ting Zhu

{"title":"Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.","authors":"Bao Ting Zhu","doi":"10.1093/jmcb/mjaf041","DOIUrl":"10.1093/jmcb/mjaf041","url":null,"abstract":"The mechanism underlying the selective loss of dopaminergic neurons in Parkinson's disease (PD) is still not understood at present. MPTP, an illicit drug contaminant, can selectively induce parkinsonism in humans and animals which is very similar to idiopathic PD. Like MPTP, 6-hydroxydopamine (6-OHDA) is another neurotoxicant also capable of selectively inducing parkinsonism in animal models. In this paper, a unifying hypothesis is proposed, which offers a plausible explanation for the pathogenic mechanism of parkinsonism induced by MPTP and 6-OHDA. This hypothesis has three core elements. (i) The vesicular monoamine transporter 2 (VMAT2) is the transporter responsible for the reverse transport (efflux) of the misplaced cytosolic dopamine (DA). (ii) Activation of VMAT2-mediated DA reverse transport is caused by elevated oxidative stress, often resulting from the buildup of cytosolic DA in dopaminergic neurons. (iii) VMAT2 is a major target of MPP+ (a toxic metabolite of MPTP) and 6-OHDA, and inhibition of VMAT2-mediated DA reverse transport by MPP+ or 6-OHDA will result in the buildup of cytosolic DA, and its subsequent oxidation/auto-oxidation will further heighten oxidative stress and generate chemically-reactive, neurotoxic DA derivatives. These DA-associated oxidative changes jointly contribute to the selective injury to dopaminergic neurons and the induction of parkinsonism. This mechanistic hypothesis agrees with a large body of experimental observations, and also offers a mechanistic explanation for many experimental findings. Additionally, this hypothesis offers mechanistic insights into the pathogenic role of α-synuclein in human PD based on its strong ability to suppress VMAT2-mediated DA reverse transport in dopaminergic neurons.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAMPT improves high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) via the SIRT1-C/EBPβ-STEAP4-NRF2 axis. NAMPT通过SIRT1-C/ ebp - β- steap4 - nrf2轴改善高脂肪饮食诱导的非酒精性脂肪性肝病（NAFLD）。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-03 DOI: 10.1093/jmcb/mjaf045

Jingwu Zhao, Qinjin Li, Yi Wang, Bingbing Liu, Sisi Gui, Yazhen Zheng, Xiaodong Chen

{"title":"NAMPT improves high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) via the SIRT1-C/EBPβ-STEAP4-NRF2 axis.","authors":"Jingwu Zhao, Qinjin Li, Yi Wang, Bingbing Liu, Sisi Gui, Yazhen Zheng, Xiaodong Chen","doi":"10.1093/jmcb/mjaf045","DOIUrl":"10.1093/jmcb/mjaf045","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic condition, yet therapeutic targets remain elusive. Nicotinamide phosphoribosyl transferase (NAMPT) and six-transmembrane epithelial antigen of the prostate 4 (STEAP4) are integral regulators in various metabolic disorders. This study investigates the role and molecular mechanisms of NAMPT in NAFLD pathogenesis. We found that inhibiting NAMPT or silent information regulator 1 (SIRT1) exacerbates liver steatosis and impairs hepatic antioxidant defenses in high-fat diet (HFD)-induced obese mice, while reducing STEAP4 expression in liver tissues, suggesting that NAMPT and SIRT1 are pivotal in NAFLD progression and may regulate STEAP4. The role of NAMPT in SIRT1 expression involves nicotinamide adenine dinucleotide synthesis. Our results indicate that inhibiting SIRT1's deacetylase activity impairs CCAAT/enhancer-binding protein β (C/EBPβ) deacetylation and consequently its function. Additionally, STEAP4, previously identified as a C/EBPβ target, can upregulate the expression and nuclear translocation of NF-E2-related factor 2 (NRF2) to combat oxidative stress in NAFLD. This study confirms that NAMPT ameliorates NAFLD via the SIRT1-C/EBPβ-STEAP4-NRF2 signaling axis in HFD-induced obese mice, proposing a novel strategy for the prevention and treatment of NAFLD.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Canonical Wnt signaling affects calcium homeostasis in serum-treated AC16 cells through MLN-mediated SERCA2a regulation. 典型Wnt信号通过mln介导的SERCA2a调控影响血清处理的AC16细胞的钙稳态。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-03 DOI: 10.1093/jmcb/mjaf050

Ang Li, Yuanyuan Shen, Zhenyan Li, Wenyu Jiang, Jie Su, Xiaomin Song, Lin Li

{"title":"Canonical Wnt signaling affects calcium homeostasis in serum-treated AC16 cells through MLN-mediated SERCA2a regulation.","authors":"Ang Li, Yuanyuan Shen, Zhenyan Li, Wenyu Jiang, Jie Su, Xiaomin Song, Lin Li","doi":"10.1093/jmcb/mjaf050","DOIUrl":"10.1093/jmcb/mjaf050","url":null,"abstract":"The canonical Wnt/β-catenin pathway critically regulates cardiac calcium homeostasis, yet its interplay with microenvironmental factors remains unclear. This study reveals that fetal bovine serum (FBS) treatment alters Wnt-mediated calcium dynamics in AC16 cardiomyocytes. While Wnt activation elevates cytosol calcium in serum-free conditions, FBS supplementation reverses this response: Wnt inhibitors (SFRP2, XAV939, and LF3) induce cytosol calcium accumulation, while the activators (LiCl and Wnt3a) lose efficacy. Mechanistically, FBS ablates RyR2 expression, uncoupling calcium-induced calcium release. Consequently, calcium handling shifts to SERCA2a-dependent regulation. We identify myoregulin (MLN) as a pivotal effector of Wnt/β-catenin signaling, with Wnt inhibition upregulating MLN to suppress SERCA2a activity. MLN knockdown (90% suppression) abolishes the effects of Wnt inhibitors on SERCA2a function and calcium distribution patterns. RyR2 reconstitution in FBS-treated cells restores calcium release but not Wnt activation responses, confirming the dominant role of MLN. Crucially, a combination of RyR2 overexpression and MLN depletion fully restores Wnt-calcium responses, phenocopying serum-free conditions. Our work establishes a serum-dependent regulatory axis where Wnt/β-catenin signaling maintains calcium homeostasis by repressing MLN, thereby preserving SERCA2a function. This FBS-induced shift mirrors pathological adaptations in heart failure, positioning MLN as a therapeutic target for calcium-handling disorders.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comments on 'BAF60a-dependent chromatin remodeling preserves β-cell function and contributes to the therapeutic benefits of GLP-1R agonists'. “baf60a依赖性染色质重塑保留β细胞功能，有助于GLP-1R激动剂的治疗效果”。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-03 DOI: 10.1093/jmcb/mjaf044

Qingqian Wu, Yue Gao, Zhuo-Xian Meng

引用次数: 0

β-alanine alleviates gout by inhibiting NLRP3 inflammasome activation. β-丙氨酸通过抑制NLRP3炎性体激活来缓解痛风。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-04-01 DOI: 10.1093/jmcb/mjag004

Xia-Ying Chen, Peng-Peng Zhu, Yuan Ying, Min-Yi Feng, Yu-Qin Xu, Liu-Bing Yu, Wen Xue, Yu Yu, Tao Li, Tao Zhou

引用次数: 0

NAD+ subcellular partitioning mediated by miR-183 and miR-96 regulates muscle stem cell differentiation. miR-183和miR-96介导的NAD+亚细胞分配调节肌肉干细胞分化。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-03-31 DOI: 10.1093/jmcb/mjag015

Mei Ma, Ruisen Ma, Zhuoyang Li, Siyi Shen, Wenqing Kong, Tianyuan Qiu, Zhoumin Niu, Jingjing Chen, Yuting Wu, Yan Li, Zi-Bing Jin, Yuying Li, Hao Ying

{"title":"NAD+ subcellular partitioning mediated by miR-183 and miR-96 regulates muscle stem cell differentiation.","authors":"Mei Ma, Ruisen Ma, Zhuoyang Li, Siyi Shen, Wenqing Kong, Tianyuan Qiu, Zhoumin Niu, Jingjing Chen, Yuting Wu, Yan Li, Zi-Bing Jin, Yuying Li, Hao Ying","doi":"10.1093/jmcb/mjag015","DOIUrl":"https://doi.org/10.1093/jmcb/mjag015","url":null,"abstract":"The intracellular abundance of NAD+, a vital metabolic cofactor, critically influences muscle stem cell (MuSC) function. However, the spatial regulation of NAD+ and its impact on MuSC function remain unclear. In this study, we demonstrated that the loss of miR-183 and miR-96 leads to inefficient skeletal muscle regeneration upon injury and triggers premature differentiation of MuSC-derived primary myoblasts. The underlying mechanism involves miRNA-mediated regulation through targeting SLC25A51, a mitochondrial transporter for NAD+ that elevates mitochondrial NAD+ while reducing cytoplasmic NAD+ levels. Our results suggest that the reduction in cytoplasmic NAD+ diminishes SIRT1-mediated deacetylation, increasing H4K16ac at the promoters of myogenic genes to promote differentiation. Concurrently, the mitochondrial NAD+ accumulation stimulates the tricarboxylic acid cycle, leading to elevated levels of ATP and citrate. These metabolites allosterically activate the ACLY pathway, which in turn increases acetyl-CoA production, thereby supplying acetyl groups for H4K16ac. Furthermore, SIRT3 knockdown impaired myogenic differentiation and attenuated the increased levels of both ATP and acetyl-CoA in miR-183/96-deficient cells, suggesting that the elevated mitochondrial NAD+ also enhances differentiation via SIRT3-mediated regulation of mitochondrial metabolism and acetyl-CoA production. Our work establishes miR-183 and miR-96 as critical regulators of epigenetic-metabolic networks that influence MuSC differentiation through subcellular partitioning of NAD+, ensuring proper regeneration timing.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclin B3 dsRNA Orchestrate Meiotic Progression in Porcine Oocytes. 细胞周期蛋白B3 dsRNA调控猪卵母细胞减数分裂进程。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-03-24 DOI: 10.1093/jmcb/mjag014

Yanlong Zhu, Xi-Qing Jiang, Shuang Gao, Chen-Yuan Zhang, Hongshuang Xie, Qingbo Yang, Zi-Hao Wang, Zhuang Chai, Zhonghua Liu, Jing-Tao Sun, Tianyao He, Jiaqiang Wang, Jun-Xue Jin

{"title":"Cyclin B3 dsRNA Orchestrate Meiotic Progression in Porcine Oocytes.","authors":"Yanlong Zhu, Xi-Qing Jiang, Shuang Gao, Chen-Yuan Zhang, Hongshuang Xie, Qingbo Yang, Zi-Hao Wang, Zhuang Chai, Zhonghua Liu, Jing-Tao Sun, Tianyao He, Jiaqiang Wang, Jun-Xue Jin","doi":"10.1093/jmcb/mjag014","DOIUrl":"https://doi.org/10.1093/jmcb/mjag014","url":null,"abstract":"Cyclin B3 (CCNB3) plays a critical regulatory role in mammalian meiosis. Studies in mice have demonstrated that CCNB3 interacts with CDK1 to modulate the activity of MPF, thereby driving meiotic progression. However, the functional mechanisms of CCNB3 in porcine oocytes remain unclear. In this study, we reveal for the first time that knockdown of CCNB3 in porcine oocytes induces meiotic arrest at metaphase I, accompanied by impaired degradation of cyclin B1 and securin. Further investigation identifies that the antisense long non-coding RNA CCNB3-AS forms a double-stranded RNA (dsRNA) structure with the CCNB3 mRNA, significantly enhancing its stability by resisting PAT1 homolog 1 (PATL1)-mediated degradation. Mechanistically, CCNB3-AS interacts with the scaffold protein Vimentin (VIM). Structural analysis reveals that VIM binds to the PAT1 domain of PATL1 and is capable of influencing the ability of CNOT7, the core subunit of the CCR4-NOT complex, to bind to PATL1, ultimately maintaining stable CCNB3 mRNA expression. Our study elucidates the molecular mechanism by which the CCNB3-AS/CCNB3 dsRNA duplex cooperates with VIM and PATL1 to collectively regulate meiosis in porcine oocytes. Furthermore, we reveal the non-canonical role of VIM in mRNA degradation, providing new theoretical support for understanding the mechanisms underlying porcine oocyte meiosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A high-content phenotypic screen identifies luteolin as a repurposed drug to reduce pyruvate dehydrogenase phosphorylation and enhance energy production in CMTX6 cell models. 在CMTX6细胞模型中，高含量表型筛选鉴定木犀草素是一种减少丙酮酸脱氢酶磷酸化和增强能量产生的重新用途药物。

IF 5.9 2区生物学

Journal of Molecular Cell Biology Pub Date : 2026-03-23 DOI: 10.1093/jmcb/mjag012

Gonzalo Perez-Siles, Masahiro Nishide, Melina Ellis, Richard M Wynn, Gauri Shishodia, Steve Vucic, Marina L Kennerson

引用次数: 0