Biochimica et biophysica acta. Molecular cell research最新文献_第8页

Loss of Prominin 2 expression inhibits AKT/mTOR signaling to limit glycolysis and drive ferroptosis in breast cancer cells 在乳腺癌细胞中，pronin2表达缺失可抑制AKT/mTOR信号通路限制糖酵解并驱动铁下垂。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-08-14 DOI: 10.1016/j.bbamcr.2025.120047

Lei Yin , Yanze Lin , Zhongdian Yuan , Rexiati Ruze , Zhen Yang , Yingmei Shao

This study aimed to characterize the oncogenic functions of Prominin 2 (PROM2), the pro-cancer and ferroptosis resistance gene, in breast cancer (BC). PROM2 expression was analyzed using single-cell RNA sequencing and the TCGA database. Its expression was confirmed in BC tissues and cell lines using qRT-PCR, immunohistochemistry, and western blot assays. The effects of PROM2 were evaluated in vivo and in vitro. RNA sequencing and GSEA were used to investigate the potential underlying molecular mechanisms of PROM2 in BC. Co-immunoprecipitation was used to determine the interaction between AKT and PROM2. PROM2 expression was elevated in clinical samples and BC cells and positively correlated with a worse prognosis. Functional experiments demonstrated that PROM2 silencing suppressed tumor growth and malignancy. Mechanistically, PROM2 interacts with AKT to activate mTOR signaling, thereby promoting glycolysis and inhibiting ferroptosis. Specifically, for glycolysis, PROM2 silencing decreased glucose uptake, extracellular acidification rate, lactate production, and glycolysis-related enzyme expression, while increasing oxygen consumption. For ferroptosis, PROM2 silencing upregulated reactive oxygen species, malondialdehyde, iron, Fe²⁺, and downregulated SLC7A11, GPX4, and glutathione levels. Overexpression of AKT or the AKT agonist (SC79) reversed the effects of PROM2 silencing on BC cell glycolysis and ferroptosis. Our results suggest that PROM2 is an oncogenic gene that supports BC progression by enhancing glycolysis and inhibiting ferroptosis via AKT/mTOR signaling. Therefore, PROM2 may be a potential therapeutic target for BC treatment.

本研究旨在探讨promein 2 （PROM2）在乳腺癌（BC）中的促癌和抗铁下垂基因的致癌功能。利用单细胞RNA测序和TCGA数据库分析PROM2的表达。通过qRT-PCR、免疫组织化学和western blot检测证实其在BC组织和细胞系中的表达。在体内和体外评价PROM2的作用。利用RNA测序和GSEA研究了PROM2在BC中的潜在分子机制。共免疫沉淀法测定AKT与PROM2的相互作用。PROM2在临床样本和BC细胞中的表达升高，并与较差的预后呈正相关。功能实验表明，PROM2沉默抑制肿瘤生长和恶性。机制上，PROM2与AKT相互作用激活mTOR信号，从而促进糖酵解，抑制铁下垂。具体来说，对于糖酵解，PROM2沉默降低了葡萄糖摄取、细胞外酸化速率、乳酸生成和糖酵解相关酶的表达，同时增加了氧气消耗。对于铁死亡，PROM2沉默上调活性氧、丙二醛、铁、Fe2+，下调SLC7A11、GPX4和谷胱甘肽水平。AKT或AKT激动剂（SC79）的过表达逆转了PROM2沉默对BC细胞糖酵解和铁凋亡的影响。我们的研究结果表明，PROM2是一种致癌基因，通过AKT/mTOR信号通路促进糖酵解和抑制铁凋亡，从而支持BC的进展。因此，PROM2可能是BC治疗的潜在治疗靶点。

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引用次数: 0

ESCO2 drives breast cancer proliferation and metastasis through PI3K/AKT/mTOR phosphorylation: A potential therapeutic target ESCO2通过PI3K/AKT/mTOR磷酸化驱动乳腺癌增殖和转移：一个潜在的治疗靶点

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-08-10 DOI: 10.1016/j.bbamcr.2025.120043

Pingchuan Li , Lineng Wei , Meng Li , Huawei Yang

Breast cancer remains a major global health threat to women, underscoring the urgent need for novel therapeutic targets. While ESCO2, an essential cell cycle regulator, has been implicated in cancer progression, its precise role and molecular mechanisms in breast cancer remain poorly understood. In this study, we first demonstrated significant upregulation of ESCO2 in breast cancer through analysis of TCGA and GEO datasets, which was further validated in clinical specimens and cell lines, with its expression correlating with advanced T-stage, aggressive molecular subtypes and poor prognosis. Functional studies in MDA-MB-231 and MDA-MB-468 cells revealed that ESCO2 overexpression promoted cell proliferation, migration and invasion, while its knockdown exerted opposite effects. Mechanistic investigations uncovered that ESCO2 depletion reduced phosphorylation of PI3K/AKT/mTOR pathway components, and co-immunoprecipitation assays confirmed direct interaction between ESCO2 and PI3K. Importantly, the tumor-suppressive effects of ESCO2 knockdown could be rescued by SC79-mediated AKT activation. In vivo experiments using xenograft mouse models consistently showed that ESCO2 silencing significantly inhibited tumor growth, increased apoptosis and necrosis, and reduced metastasis. Collectively, our findings establish ESCO2 as a novel oncogene driving breast cancer progression through PI3K/AKT/mTOR pathway activation, highlighting its potential as a promising therapeutic target for breast cancer intervention.

乳腺癌仍然是全球妇女面临的主要健康威胁，因此迫切需要寻找新的治疗靶点。虽然ESCO2是一种重要的细胞周期调节剂，与癌症进展有关，但其在乳腺癌中的确切作用和分子机制仍知之甚少。在本研究中，我们首先通过TCGA和GEO数据集的分析证实了ESCO2在乳腺癌中的显著上调，并在临床标本和细胞系中进一步验证，其表达与晚期t期、侵袭性分子亚型和不良预后相关。对MDA-MB-231和MDA-MB-468细胞的功能研究表明，ESCO2过表达促进细胞增殖、迁移和侵袭，而其敲低则相反。机制研究发现，ESCO2消耗降低了PI3K/AKT/mTOR通路组分的磷酸化，共免疫沉淀实验证实了ESCO2和PI3K之间的直接相互作用。重要的是，ESCO2敲除的肿瘤抑制作用可以通过sc79介导的AKT激活来恢复。异种移植小鼠模型的体内实验一致表明，ESCO2沉默显著抑制肿瘤生长，增加细胞凋亡和坏死，减少转移。总之，我们的研究结果表明，ESCO2是一种通过激活PI3K/AKT/mTOR通路驱动乳腺癌进展的新型癌基因，突出了其作为乳腺癌干预治疗靶点的潜力。

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引用次数: 0

Prolyl isomerase Pin4 impacts estrogen receptor transactivation by enhancing phosphorylation and consequently promotes the proliferation of breast cancer cells 脯氨酸异构酶Pin4通过增强磷酸化影响雌激素受体的反活化，从而促进乳腺癌细胞的增殖。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-08-10 DOI: 10.1016/j.bbamcr.2025.120044

Masa-Ki Inoue , Rena Ueda , Mikako Nakanishi , Machi Kanna , Yasuka Matsunaga , Tomoichiro Asano , Yusuke Nakatsu

Breast cancer is the most common tumor in women, and approximately 70 % of cases are diagnosed to be estrogen receptor α (ERα)-positive. Estradiol (E2)-ERα signaling is undoubtedly involved in the development of breast cancer, and the upregulation of this pathway is linked to tamoxifen resistance. However, ERα regulation is complex, and the underlying mechanisms have not been comprehensively elucidated.

Pin4 is a prolyl isomerase that promotes cis-trans isomerization of proline residues. Although its role remains unclear, an analysis of public databases reveals that Pin4 expression in breast cancer tissues is higher than that in normal tissues.

Here, we reveal that Pin4 regulates ERα transcriptional activity and is essential for the proliferation of ERα-positive breast cancer cells. In MCF7 and T47D cells, Pin4 knockdown drastically decreased cell proliferation by inducing cell cycle arrest. In addition, the silencing of Pin4 impaired the expression of E2-induced genes, including E2F1. We also found that Pin4 interacted with ERα and affected its transcriptional activity by promoting phosphorylation at Ser167, which was involved in the recruitment of steroid receptor coactivator-3 (SRC-3) into ERα. Importantly, the silence of Pin4 gene in T47D cells attenuated the interaction between SRC-3 and ERα.

Collectively, the study findings show that Pin4 is a critical factor in the development of ERα-positive breast cancers and the identification of Pin4 inhibitors could be a promising therapeutic strategy.

乳腺癌是女性中最常见的肿瘤，大约70% %的病例被诊断为雌激素受体α (ERα)阳性。雌二醇(E2)-ERα信号无疑参与了乳腺癌的发展，该信号通路的上调与它莫昔芬耐药性有关。然而，ERα调控是复杂的，其潜在机制尚未全面阐明。Pin4是一种促进脯氨酸残基顺反异构化的脯氨酸异构酶。尽管其作用尚不清楚，但对公共数据库的分析显示，Pin4在乳腺癌组织中的表达高于正常组织。在这里，我们发现Pin4调节ERα转录活性，并且对于ERα阳性乳腺癌细胞的增殖至关重要。在MCF7和T47D细胞中，Pin4敲低通过诱导细胞周期阻滞而显著降低细胞增殖。此外，Pin4的沉默会损害e2诱导基因的表达，包括E2F1。我们还发现Pin4与ERα相互作用，并通过促进Ser167的磷酸化影响ERα的转录活性，这参与了类固醇受体共激活因子-3 （SRC-3）向ERα的募集。重要的是，T47D细胞中Pin4基因的沉默减弱了SRC-3与ERα的相互作用。总的来说，研究结果表明，Pin4是er α阳性乳腺癌发展的关键因素，鉴定Pin4抑制剂可能是一种有前景的治疗策略。

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引用次数: 0

Hyperosmolarity-induced activation of PIEZO1 engages detrimental calcium/oxidative stress signaling and adaptive catalase response in renal inner medullary collecting duct (mIMCD3) cells 高渗透压诱导的PIEZO1激活在肾髓内收集管（mIMCD3）细胞中参与有害的钙/氧化应激信号和适应性过氧化氢酶反应。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-08-07 DOI: 10.1016/j.bbamcr.2025.120041

Stephanie Probst , Nadiya Romanova , Robin Herbrechter , Teresa Kern , Marie Bergmeier , Wing-Kee Lee , Frank Thévenod

The collecting duct (CD) is the final segment of the renal nephron and is involved in the fine regulation of osmotic and ionic homeostasis. Its medullary segment is continuously exposed to a wide spectrum of osmotic gradients and resultant osmotic stress. Strikingly, the expression of the mechanically activated non-selective cationic and Ca²⁺-permeable transduction ion channel PIEZO1 is most prominent in inner medullary CD (IMCD) cells, yet its functions there are still not well understood. We hypothesized increased PIEZO1 expression in the IMCD could be linked to its hyperosmotic stress environment. Using the mouse mIMCD₃ cell line, which has been used to characterize hyperosmotic stress-induced cell death, we demonstrate twice as much PIEZO1 expression compared to proximal tubule (WKPT-0293 Cl.2) or cortical CD (mCCD(cl.1)) cell lines. Hyperosmolarity/−tonicity by addition of NaCl ± urea to the culture medium (+ 100–300 mosmol/l) or PIEZO1 agonist Yoda1 (20 μmol/l) decreased mIMCD₃ cell viability assayed by MTT, which were antagonized by PIEZO1 inhibitors GsMTx4 (2.5 μmol/l) and salvianolic acid (SalB, 10 μmol/l). PIEZO1 activation by hyperosmolarity and agonists (Yoda1, Jedi1) increased Ca²⁺ influx, downstream reactive oxygen species (ROS), in particular mitochondrial superoxide (O₂^•-) formation, and subsequent adaptive ROS-decomposing catalase expression and activity that were sensitive to PIEZO1 antagonists (GsMTx4, SalB). Hence, the data demonstrate hyperosmolarity/−tonicity of the kidney elicits PIEZO1 activation, mitochondrial ROS formation and cell death that are partially countered by catalase-mediated stress adaptation.

集合管是肾元的最后一段，参与渗透和离子稳态的精细调节。它的髓质段持续暴露于广泛的渗透梯度和由此产生的渗透应力。引人注目的是，机械激活的非选择性阳离子和Ca2+渗透性转导离子通道PIEZO1的表达在髓内CD （IMCD）细胞中最为突出，但其功能仍未得到很好的理解。我们假设在IMCD中增加的PIEZO1表达可能与其高渗应激环境有关。使用小鼠mIMCD3细胞系（已用于表征高渗应激诱导的细胞死亡），我们证明PIEZO1的表达量是近端小管（WKPT-0293 Cl.2）或皮质CD（mCCD(cl.1)）细胞系的两倍。采用MTT法测定，在培养基（+100-300 μmol/l）或PIEZO1激动剂Yoda1（20 μmol/l）中加入NaCl±尿素的高渗透性/-强直性可降低mIMCD3细胞活力，而PIEZO1抑制剂GsMTx4（2.5 μmol/l）和丹酚酸（SalB, 10 μmol/l）可拮抗细胞活力。高渗透压和激动剂（Yoda1, Jedi1）激活PIEZO1会增加Ca2+内流，下游活性氧（ROS），特别是线粒体超氧化物（O2•-）的形成，以及随后对PIEZO1拮抗剂（GsMTx4, SalB）敏感的适应性ROS分解过氧化氢酶的表达和活性。因此，数据表明，肾脏的高渗透压/-强直性引发PIEZO1激活，线粒体ROS形成和细胞死亡，部分被过氧化氢酶介导的应激适应所抵消。

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引用次数: 0

Insights into early cochlear damage induced by potassium channel deficiency 钾通道缺乏致早期耳蜗损伤的研究进展。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-08-05 DOI: 10.1016/j.bbamcr.2025.120030

Ezequiel Rías , Camila Carignano , Valeria C. Castagna , Leonardo Dionisio , Jimena A. Ballestero , Giuliana Paolillo , Ingrid Ouwerkerk , María Eugenia Gomez-Casati , Guillermo Spitzmaul

Hearing loss (HL) is the most common sensory disorder, caused by genetic mutations and acquired factors like presbycusis and noise exposure. A critical factor in HL development is the dysfunction of potassium (K⁺) channels, essential for sensory cell function in the organ of Corti (OC). Inner and outer hair cells (IHCs and OHCs) convert sound into electrical signals, while supporting cells (SCs) maintain ionic and structural balance. KCNQ4 channels, located in the basal membrane of OHCs, regulate K⁺ efflux. Mutations in KCNQ4 are linked to progressive HL (DFNA2), noise-induced hearing loss, and presbycusis, leading to K⁺ accumulation, cellular stress, and OHC death. Gene editing or pharmacological activation of KCNQ4 has shown potential in partially preventing HL in mouse models. In this study, we demonstrate KCNQ4 deletion disrupts the localization of key proteins like prestin and BK channels, alters OHC organization, and induces apoptosis in sensory and SC. Spiral ganglion neurons (SGNs) also degenerate over time. Despite these structural changes, noise exposure does not exacerbate OHC damage in our KCNQ4-deficient model. This highlights KCNQ4's role in maintaining ion homeostasis and cochlear function, as its absence triggers widespread dysfunction in the OC. The present study demonstrates that disruptions in a single cell type can have a cascade effect on overall cochlear health. Understanding the molecular and cellular consequences of KCNQ4 mutations is crucial for developing targeted therapies to mitigate progressive HL caused by genetic and environmental factors.

听力损失（HL）是最常见的感觉障碍，由基因突变和获得性因素如老年性耳聋和噪音暴露引起。HL发展的一个关键因素是钾（K+）通道的功能障碍，这对Corti器官（OC）的感觉细胞功能至关重要。内外部毛细胞（IHCs和OHCs）将声音转化为电信号，而支持细胞（SCs）维持离子和结构平衡。KCNQ4通道位于OHCs基膜，调节K+外排。KCNQ4突变与进行性HL （DFNA2）、噪声性听力损失和老年性耳聋有关，导致K+积累、细胞应激和OHC死亡。在小鼠模型中，基因编辑或药理激活KCNQ4已显示出部分预防HL的潜力。在这项研究中，我们证明KCNQ4缺失会破坏prestin和BK通道等关键蛋白的定位，改变OHC组织，诱导感觉和SC的凋亡。螺旋神经节神经元（sgn）也会随着时间的推移而退化。尽管存在这些结构变化，但在kcnq4缺陷模型中，噪声暴露不会加剧OHC损伤。这突出了KCNQ4在维持离子稳态和耳蜗功能中的作用，因为它的缺失会引发耳蜗OC中广泛的功能障碍。目前的研究表明，单个细胞类型的破坏可以对整个耳蜗健康产生级联效应。了解KCNQ4突变的分子和细胞后果对于开发靶向治疗以减轻由遗传和环境因素引起的进行性HL至关重要。

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引用次数: 0

MicroRNA-22-3p suppresses hair regrowth in androgenetic alopecia by targeting chloride intracellular channel 4 MicroRNA-22-3p通过靶向氯离子胞内通道4抑制雄激素性脱发的毛发再生

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-07-31 DOI: 10.1016/j.bbamcr.2025.120033

Haijing Fu , Chenxi Wu , Tianyi Xu , Wumei Zhao , Leiwei Jiang , Shijun Shan

Androgenetic alopecia (AGA), the most prevalent form of patterned hair loss, manifests through androgen sensitivity, age-dependent progression, and genetic predisposition. Emerging evidence highlights microRNAs as critical post-transcriptional regulators in hair follicle pathophysiology. This study used human hair follicle stem cells (HFSCs), hair follicle samples of AGA patients and AGA mouse model to explore the role of miR-22-3p/CLIC4 signaling in AGA. A significant rise in miR-22-3p expression was observed in balding hair follicles of grade 5 AGA patients. Then we identify chloride intracellular channel 4 (CLIC4) as a novel target of miR-22-3p and CLIC4 is markedly low expressed in balding hair follicle of AGA patients. Functional studies demonstrated that knockdown CLIC4 (shCLIC4) impaired HFSCs proliferative capacity and disrupted sonic hedgehog (SHH) pathway activation, evidenced by decreased Gli1 and Gli2 transcriptional activity. These findings establish the miR-22-3p/CLIC4 axis as a novel regulator of hair follicular miniaturization, proposing CLIC4-mediated SHH modulation as a potential therapeutic target for AGA intervention.

雄激素性脱发（AGA）是最常见的斑秃形式，表现为雄激素敏感性、年龄依赖性进展和遗传易感性。新出现的证据表明，microRNAs在毛囊病理生理中是关键的转录后调节因子。本研究利用人毛囊干细胞（HFSCs）、AGA患者毛囊样本和AGA小鼠模型，探讨miR-22-3p/CLIC4信号通路在AGA中的作用。在5级AGA患者的秃顶毛囊中观察到miR-22-3p的表达显著升高。然后，我们确定了氯离子细胞内通道4 （CLIC4）作为miR-22-3p的新靶点，并且CLIC4在AGA患者的秃顶毛囊中明显低表达。功能研究表明，敲低CLIC4 （shCLIC4）会损害HFSCs的增殖能力，破坏sonic hedgehog （SHH）通路的激活，这可以通过Gli1和Gli2转录活性降低来证明。这些发现确立了miR-22-3p/CLIC4轴作为毛囊小型化的新调节因子，提出了CLIC4介导的SHH调节作为AGA干预的潜在治疗靶点。

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引用次数: 0

SYT13: An underestimated synaptotagmin SYT13：一种被低估的突触联合蛋白

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-07-30 DOI: 10.1016/j.bbamcr.2025.120031

Johannes Lehmann , Alberto Catanese

Synaptotagmin-13 (SYT13) is a non-canonical member of the of synaptotagmin family that, canonical synaptotagmins, doesn't contain Ca²⁺ binding sites, but still appears to play a key role in the control of different cellular processes such as vesicle transport, cell migration, signaling and cell development. The recent findings associate SYT13 with neuronal survival and development, metabolic homeostasis (especially insulin secretion) and both oncogenic and tumor suppressive function in multiple cancers. And yet all this data is scattered in fields, with no systematic review covering SYT13's detailed biology. A comprehensive literature review is therefore needed to explain SYT13's multifaceted roles, uncover informational gaps and direct future studies to exploit SYT13 as a target for neurodegeneration, metabolic disease and cancer therapy.

SYT13 （synaptotagmin -13）是synaptotagmin家族的非规范成员，不含Ca2+结合位点，但仍在控制不同的细胞过程中发挥关键作用，如囊泡运输、细胞迁移、信号传导和细胞发育。最近的研究结果将SYT13与多种癌症的神经元存活和发育、代谢稳态（特别是胰岛素分泌）以及致癌和肿瘤抑制功能联系起来。然而，所有这些数据都分散在各个领域，没有对SYT13的详细生物学进行系统回顾。因此，需要全面的文献综述来解释SYT13的多方面作用，揭示信息空白，并指导未来的研究，以利用SYT13作为神经退行性疾病、代谢性疾病和癌症治疗的靶点。

引用次数: 0

HMGB1 activates caspase-1 and induces hepatic stellate cell activation via GABPA-ASC HMGB1激活caspase-1，通过GABPA-ASC诱导肝星状细胞活化

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-07-30 DOI: 10.1016/j.bbamcr.2025.120032

Mengjia Jing , Yixing Luo , Lumiao Zhang , Yu Fu , Wei Yan

In the intricate process leading to liver fibrosis, which frequently correlates with inflammation, the activation of hepatic stellate cells (HSCs) is critical. High mobility group box 1(HMGB1), as endogenous danger signal in the extracellular environment, governs the activation of caspase-1 and hepatic stellate cell. Constructing a liver fibrosis model via intraperitoneal thioacetamide (TAA) administration unveiled excessive HMGB1 expression and serum release during the TAA-induced fibrosis progression. Intraperitoneal injection of ethyl pyruvate (EP, which inhibits the release of HMGB1) or AAV-shHMGB1 can significantly reverse the progression of liver fibrosis induced by TAA. Recombinant HMGB1 (rHMGB1) and Z-YVAD-FMK (Caspase-1 inhibitor) were used to treat HSCs. It was found that HMGB1 could activate caspase-1, while Z-YVAD-FMK could prevent HMGB1-induced activation of HSCs. Through immunofluorescence, immunoblotting, lentiviral transfection, luciferase reporter assay and chromatin immunoprecipitation assay, it was found that HMGB1 activated caspase-1 through GABPA-regulated ASC transcription, which not only participates in the activation of caspase-1, but also promotes the process of liver fibrosis. Taken together, HMGB1 significantly drives HSC activation. It boosts ASC transcriptional activity via GABPA leading to caspase-1 activation and fostering liver fibrosis development.

肝纤维化通常与炎症相关，在导致肝纤维化的复杂过程中，肝星状细胞（hsc）的激活至关重要。高迁移率组框1（HMGB1）作为细胞外环境中的内源性危险信号，调控caspase-1和肝星状细胞的激活。通过腹腔注射硫代乙酰胺（TAA）构建肝纤维化模型，揭示了TAA诱导的肝纤维化过程中HMGB1的过度表达和血清释放。腹腔注射抑制HMGB1释放的丙酮酸乙酯（EP）或AAV-shHMGB1可显著逆转TAA诱导的肝纤维化进展。采用重组HMGB1 （rHMGB1）和Z-YVAD-FMK （Caspase-1抑制剂）治疗hsc。发现HMGB1可以激活caspase-1，而Z-YVAD-FMK可以阻止HMGB1诱导的hsc活化。通过免疫荧光、免疫印迹、慢病毒转染、荧光素酶报告基因实验、染色质免疫沉淀实验发现，HMGB1通过gabpa调控ASC转录激活caspase-1，不仅参与caspase-1的激活，而且促进肝纤维化过程。综上所述，HMGB1显著驱动HSC活化。它通过GABPA促进ASC转录活性，导致caspase-1激活并促进肝纤维化的发展。

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引用次数: 0

Corrigendum to “USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression” [Volume 1872, Issue 7, October 2025, 120004] “USP47增强nrp1介导的血管生成以促进胃癌进展”的勘误表[1872卷，第7期，2025年10月，120004]。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-07-23 DOI: 10.1016/j.bbamcr.2025.120025

Wei Chen , Huizhi Wang , Haitao Sun , Junbo Zuo , Pengcheng Jiang , Wen Feng , Zhenhua Huang

引用次数: 0

XCL1: a multifunctional chemokine with metamorphic properties and therapeutic potential after injury to the nervous system – review XCL1：一种具有神经系统损伤后变质特性和治疗潜力的多功能趋化因子。

IF 4.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2025-07-21 DOI: 10.1016/j.bbamcr.2025.120028

Agata Ciechanowska, Joanna Mika

XC Motif Chemokine Ligand 1 (XCL1, known as lymphotactin), acting via XCR1, is a member of the chemokine family which includes molecules with chemotactic functions. However, subsequent years of research on this chemokine, while simultaneously exploring and understanding the complexity of the processes taking place in living organisms, have revealed a plethora of interesting information about its properties. This review aims to combine the current knowledge on the properties of XCL1 under pathological conditions, particularly in neuropathy. We wanted to draw attention to the unusual properties of XCL1 that have not yet been considered, such as its metamorphic properties and its mutual connections with glycosaminoglycans and integrin subunit alpha 9 (ITGA9). Furthermore, given the well-documented roles of XCL1 in the coordination of homeostatic and immune responses, we anticipate that a comprehensive understanding of the molecular interactions regulating XCL1 binding and activation of its receptors may facilitate the development of novel drugs targeting XCR1 or ITGA9 in various diseases. This point of view may be of great importance in the future for the modulation of systems related to this chemokine for therapeutic applications. This review aims to outline new areas of interest, to break out of following old patterns and dead ends and to sketch further research paths.

XC Motif趋化因子配体1 （Chemokine Ligand 1, XCL1）是通过XCR1起作用的趋化因子家族的成员，该家族包括具有趋化功能的分子。然而，随后几年对这种趋化因子的研究，在探索和理解生物体中发生的过程的复杂性的同时，揭示了关于其特性的大量有趣信息。本综述旨在结合目前关于XCL1在病理条件下，特别是在神经病变中的特性的知识。我们希望引起人们对XCL1尚未被考虑的不寻常性质的注意，例如它的变质性质以及它与糖胺聚糖和整合素亚基α 9 （ITGA9）的相互联系。此外，鉴于XCL1在协调体内平衡和免疫反应中的作用，我们预计，全面了解调节XCL1结合及其受体激活的分子相互作用可能有助于开发针对各种疾病的XCR1或ITGA9的新型药物。这一观点可能是非常重要的，在未来的系统调节相关的趋化因子的治疗应用。这篇综述旨在概述新的兴趣领域，打破旧的模式和死胡同，并勾勒出进一步的研究路径。

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引用次数: 0