Cellular and Molecular Life Sciences最新文献_第5页

Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release. 有或没有GDNF释放的人间充质干细胞移植对癫痫发生的调节。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-21 DOI: 10.1007/s00018-025-05853-z

Eliška Waloschková, Esbjörn Melin, Camille Baumlin, My Andersson, Alberto Martínez Serrano, Merab Kokaia, Marco Ledri

{"title":"Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release.","authors":"Eliška Waloschková, Esbjörn Melin, Camille Baumlin, My Andersson, Alberto Martínez Serrano, Merab Kokaia, Marco Ledri","doi":"10.1007/s00018-025-05853-z","DOIUrl":"https://doi.org/10.1007/s00018-025-05853-z","url":null,"abstract":"Epilepsy is a central nervous system disorder causing uncontrollable seizures. One-third of patients do not respond to current medications, necessitating new treatments. This study targeted epileptogenesis, the process leading to chronic epilepsy, using human mesenchymal stem cells (MSCs) in a rodent model. MSC transplantation can positively affect neurodegenerative diseases by modifying inflammation. Additionally, glial cell line-derived neurotrophic factor (GDNF) may counteract seizures and tissue damage. We transplanted naïve immortalized human adipose-derived MSCs (Ctrl-MSCs) or GDNF-releasing MSCs (GDNF-MSCs, releasing 588.67 ± 20.14 pg/ml/24 h GDNF) into rat hippocampi after kainic acid-induced status epilepticus. Seizure progression was monitored for 5 weeks using video-EEG, behavioral assessments, and histological analysis. Both cell types influenced epileptogenesis. GDNF-MSCs delayed early-stage seizures, while Ctrl-MSCs reduced seizure frequency in later stages. Differences emerged in seizure development and cumulative seizure count, with Ctrl-MSCs showing significant seizure-attenuating effects. Behavioral differences were also noted: Ctrl-MSCs improved short-term memory and reduced anxiety, whereas GDNF-MSCs primarily reduced anxiety without significantly improving memory. This study highlights the therapeutic potential of MSCs, with or without GDNF, in modulating epileptogenesis, offering promising avenues for future clinical treatments.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"316"},"PeriodicalIF":6.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944870","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

Spatial protein redistribution: wandering but not lost. 空间蛋白质再分配：徘徊但不丢失。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-21 DOI: 10.1007/s00018-025-05803-9

Faiza Amterat Abu Abayed, Laila Abu Madegam, Ayelet Gilad, Gal Twito, Suad Sheikh Suliman, Suma Biadsy, Aeid Igbaria

{"title":"Spatial protein redistribution: wandering but not lost.","authors":"Faiza Amterat Abu Abayed, Laila Abu Madegam, Ayelet Gilad, Gal Twito, Suad Sheikh Suliman, Suma Biadsy, Aeid Igbaria","doi":"10.1007/s00018-025-05803-9","DOIUrl":"https://doi.org/10.1007/s00018-025-05803-9","url":null,"abstract":"Interorganellar spatial redistribution of proteins represents a critical yet underexplored facet of eukaryotic cell biology. This dynamic aspect of proteostasis allows proteins to acquire novel functions based on their subcellular localization, enabling the cell to adapt to both physiological and pathological challenges. Such spatial reprogramming is especially pronounced under stress conditions, including those associated with cancer, neurodegenerative diseases and viral infection, where widespread remodeling of the proteome facilitates survival and adaptation. Despite increasing appreciation of its biological significance, the molecular mechanisms underlying protein relocalization, as well as the functional outcomes of interorganellar trafficking, remain incompletely understood. This review highlights recent advances in the field, with a particular focus on the redistribution of proteins from the endoplasmic reticulum (ER) to other organelles. We provide a detailed examination of a recently characterized mechanism by which cytosolic and ER-resident chaperones and cochaperones mediate the extraction of proteins from the ER into the cytosol. Furthermore, we explore the fate of these relocalized proteins, the mechanistic underpinnings of their trafficking, and how this process compares with other modes of intracellular protein redistribution. Understanding these pathways offers valuable insights into fundamental cell biology and unveils new avenues for therapeutic intervention.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"315"},"PeriodicalIF":6.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944784","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

MED12 mutation induces RTK inhibitor resistance in NSCLC via MEK/ERK pathway activation by inflammatory cytokines. MED12突变通过炎症细胞因子激活MEK/ERK通路诱导非小细胞肺癌RTK抑制剂耐药。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-20 DOI: 10.1007/s00018-025-05791-w

Hyun-Min Ryu, Deokhoon Kim, Jun Young Choi, Shinkyo Yoon, Ho-Su Lee, Ji Eun Park, Eunjin Lee, Yunkyung Sung, Chang Hoon Lee, Eun-Young Lee, Wanlim Kim, Seyoung Seo, Sang-We Kim, Kang-Seo Park, Dae Ho Lee

{"title":"MED12 mutation induces RTK inhibitor resistance in NSCLC via MEK/ERK pathway activation by inflammatory cytokines.","authors":"Hyun-Min Ryu, Deokhoon Kim, Jun Young Choi, Shinkyo Yoon, Ho-Su Lee, Ji Eun Park, Eunjin Lee, Yunkyung Sung, Chang Hoon Lee, Eun-Young Lee, Wanlim Kim, Seyoung Seo, Sang-We Kim, Kang-Seo Park, Dae Ho Lee","doi":"10.1007/s00018-025-05791-w","DOIUrl":"https://doi.org/10.1007/s00018-025-05791-w","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is frequently associated with mutations in receptor tyrosine kinases (RTKs), such as EGFR and ALK. While RTK inhibitors (RTKIs) have proven effective in treating patients with specific RTK mutations, the emergence of resistance to these therapies remains a significant clinical obstacle. As such, there is still an unmet need for the identification of new biomarkers that can predict resistance to RTK inhibitors in clinical use. In the present study, we demonstrate that MED12 mutations are a key driver of RTKi resistance in NSCLC cells. This resistance is mediated through the release of inflammatory cytokines triggered by MED12 degradation. Notably, we observed that of the two major downstream signaling pathways activated by inflammatory cytokines, only the MEK/ERK pathway was upregulated, while the PI3K/AKT pathway was unaffected in MED12 knock-out (KO) cells. The degradation of MED12 results in the dissociation of the MED12 complex, which subsequently leads to YAP phosphorylation. This phosphorylated YAP increases PTEN expression by inhibiting miR-29, thereby suppressing the PI3K/AKT signaling pathway. Importantly, treatment with trametinib, a MEK inhibitor, effectively suppressed tumor growth in MED12KO NSCLC cells and in xenograft models derived from these cells. These findings suggest that targeting the MEK/ERK signaling pathway, such as with trametinib, may provide a viable strategy to overcome RTKi resistance in MED12-mutant NSCLC. Furthermore, MED12 is identified as a crucial biomarker and potential therapeutic target for overcoming RTKi resistance.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"314"},"PeriodicalIF":6.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944829","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

TRDMT1 methyltransferase gene knockout attenuates STING-based cell death signaling during self-extracellular RNA-mediated response in drug-induced senescent osteosarcoma cells. TRDMT1甲基转移酶基因敲除在药物诱导的衰老骨肉瘤细胞自我细胞外rna介导的反应中减弱STING-based细胞死亡信号。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05835-1

Gabriela Betlej, Anna Deręgowska, Maciej Wnuk, Dominika Błoniarz, Tomasz Szmatoła, Katarzyna Klimczak, Jagoda Adamczyk-Grochala, Julia Świętoń, Anna Lewińska

{"title":"TRDMT1 methyltransferase gene knockout attenuates STING-based cell death signaling during self-extracellular RNA-mediated response in drug-induced senescent osteosarcoma cells.","authors":"Gabriela Betlej, Anna Deręgowska, Maciej Wnuk, Dominika Błoniarz, Tomasz Szmatoła, Katarzyna Klimczak, Jagoda Adamczyk-Grochala, Julia Świętoń, Anna Lewińska","doi":"10.1007/s00018-025-05835-1","DOIUrl":"10.1007/s00018-025-05835-1","url":null,"abstract":"Under stress conditions, endogenous biomolecules such as nucleic acids or proteins can be released from damaged cells and considered as damage-associated molecular patterns (DAMPs) activating innate immune system and context-dependent responses. In the present study, self-extracellular RNA was obtained from dying (RNA D) and senescent (RNA S) cellular models of osteosarcoma (OS), characterized by NGS, and tested against proliferating and non-proliferating (etoposide-indued senescent) OS cells (U-2 OS, SaOS-2, MG-63, 143B). RNA D and RNA S induced apoptosis, nitro-oxidative stress, nucleic acid sensing pathways and cytokine production, and RNA m5C methyltransferase-based responses (TRDMT1 and NSUN2) in proliferating OS cells. In drug-induced senescent OS cells, TRDMT1 gene knockout (KO) prevented STING activation, related proinflammatory response, and cell death. Furthermore, IFN-β binding RNA partners were identified, namely NSUN2, NSUN5, NSUN6, CDKN1A, MYC, and RAD51 transcripts and these interactions were compromised in TRDMT1 KO cells and upon RNA D and RNA S treatment. TRDMT1 KO also resulted in replication stress in OS cells that was potentiated by RNA D and RNA S stimulation and associated with elevated levels of APOBEC3A and APOBEC3G, members of the cytidine deaminase protein family. In conclusion, we showed that TRDMT1 KO restricted STING-based immune and cell death response to RNA D and RNA S in non-proliferating drug resistant OS cells that might have potential therapeutic implications.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"310"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834218","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

RER1 regulates lipid metabolism in monocytes and macrophages. RER1调节单核细胞和巨噬细胞的脂质代谢。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05817-3

Yanxia Liu, Sandra Theil, Mohamed H Yaghmour, Anja Kerksiek, Peng Chen, Ingo G H Schmidt-Wolf, Rebecca Barker, Eva Bartok, Dieter Lütjohann, Christoph Thiele, Jochen Walter

{"title":"RER1 regulates lipid metabolism in monocytes and macrophages.","authors":"Yanxia Liu, Sandra Theil, Mohamed H Yaghmour, Anja Kerksiek, Peng Chen, Ingo G H Schmidt-Wolf, Rebecca Barker, Eva Bartok, Dieter Lütjohann, Christoph Thiele, Jochen Walter","doi":"10.1007/s00018-025-05817-3","DOIUrl":"10.1007/s00018-025-05817-3","url":null,"abstract":"Retention in endoplasmic reticulum sorting receptor 1 (RER1) mediates the retention and retrieval of select cargo proteins, and thereby regulates protein transport in the secretory pathway and assembly of distinct protein complexes. Recently, RER1 was implicated in the assembly and subcellular transport of the TREM2-DAP12 immune receptor complex, and its function in intracellular signaling and phagocytosis. However, the role of RER1 in the regulation of immune cell metabolism remained unknown. Here, we demonstrate an important role of RER1 in the lipid metabolism of monocytic and macrophage-like differentiated THP-1 cells. The deficiency of RER1 resulted in the accumulation of lipid droplets (LDs) in both monocytes and macrophage-like cells. Comprehensive mass spectrometry analyses revealed complex changes in the cellular lipid metabolism and the composition of LDs. RNA sequencing revealed an important role of RER1 in the regulation of genes related to lipid metabolism. Further, western immunoblotting confirmed an important role of RER1 in the expression of select key proteins involved in cellular lipid metabolism. The combined data indicate that RER1 plays an essential role in lipid metabolism in monocytes and macrophages.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"313"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834216","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

KRAS4B is required for placental development. KRAS4B是胎盘发育所必需的。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05846-y

Marie-Albane Minati, Leyre López Muneta, Younes Achouri, Sophie Pirenne, Corentin Porada, Francesca Rochais, Patrick Jacquemin

{"title":"KRAS4B is required for placental development.","authors":"Marie-Albane Minati, Leyre López Muneta, Younes Achouri, Sophie Pirenne, Corentin Porada, Francesca Rochais, Patrick Jacquemin","doi":"10.1007/s00018-025-05846-y","DOIUrl":"10.1007/s00018-025-05846-y","url":null,"abstract":"Beyond its well-established role in cancer, KRAS is also crucial for embryogenesis, as its absence leads to embryonic lethality. However, the precise mechanisms underlying the developmental functions of KRAS, as well as the respective roles of its two splicing isoforms, KRAS4A and KRAS4B, remain incompletely characterized. To address these issues, we generated Kras4A knock-out (Kras4A-/-) and Kras4B-/- mouse models using CRISPR/Cas9 technology, and compared their phenotypes to those of a Kras-/- model, in which both isoforms are simultaneously inactivated. We observed that Kras-/- and Kras4B-/- embryos show a lethality that starts around E13.5, while Kras4A-/- embryos develop normally, with no detectable abnormalities. In contrast, Kras-/- embryos displayed a dual phenotype affecting both the heart and placenta, whereas Kras4B-/- embryos exhibited only the placental phenotype. The cardiac phenotype was complex, combining ventricular non-compaction, ventricular septal defects, double outlet right ventricle, and overriding aorta, likely resulting from impaired cardiac precursor proliferation. The placental phenotype was characterized by reduced placental size, and a marked decrease in glycogen trophoblast cells, correlating with hypoglycemia and hypoxia in Kras-/- and Kras4B-/- embryos. Thus, our findings confirm the predominant role of KRAS4B in KRAS-mediated developmental functions, but also suggest hidden functions of KRAS4A. Importantly, this study is the first to identify KRAS as a key regulator of a specific cell differentiation process and to characterize the biological defects caused by its loss.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"308"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834214","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

Junctional adhesion molecule-C: A multifunctional mediator of cell adhesion. 连接粘附分子- c：细胞粘附的多功能介质。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05829-z

Klaus Ebnet, Michel Aurrand-Lions

引用次数: 0

Quercetin alleviates acute pancreatitis by modulating glycolysis and mitochondrial function via PFKFB3 inhibition. 槲皮素通过抑制PFKFB3调节糖酵解和线粒体功能减轻急性胰腺炎。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05845-z

Hai Jiang, Jia Liu, Zhipeng Xu, Qi Song, Junjie Tao, Heng Zhu, Qiliang Li, Lei Li

{"title":"Quercetin alleviates acute pancreatitis by modulating glycolysis and mitochondrial function via PFKFB3 inhibition.","authors":"Hai Jiang, Jia Liu, Zhipeng Xu, Qi Song, Junjie Tao, Heng Zhu, Qiliang Li, Lei Li","doi":"10.1007/s00018-025-05845-z","DOIUrl":"10.1007/s00018-025-05845-z","url":null,"abstract":"Objective: Acute pancreatitis (AP) is a severe inflammatory disease associated with dysregulated glycolysis and mitochondrial dysfunction. This study investigates the therapeutic potential of quercetin, a novel PFKFB3 inhibitor, in modulating glycolysis and mitochondrial function to alleviate AP.Methods: We conducted homology analysis of the PFKFB3 protein and identified quercetin as a potential inhibitor through molecular docking. In vitro experiments using a cerulein-induced inflammatory pancreatic cell model assessed the effects of quercetin on PFKFB3 expression, glycolysis, and mitochondrial function. In vivo validation was performed using an AP rat model to evaluate the impact on inflammation, tissue damage, and metabolic status.Results: Quercetin significantly reduced PFKFB3 expression, inhibited glycolysis, and improved mitochondrial function in inflammatory pancreatic cells. In the AP rat model, quercetin treatment decreased serum amylase and lipase levels, reduced inflammatory markers (TNF-α and IL-6), and alleviated pancreatic tissue damage, as evidenced by histological analysis.Conclusion: Quercetin effectively modulates glycolysis and mitochondrial function by inhibiting PFKFB3, thereby reducing inflammation and tissue damage in AP. These findings highlight the potential of quercetin as a novel therapeutic agent for AP.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"311"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834215","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

Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation. USP33和TAP63通过自噬和铁下垂激活协同抑制TNBC。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-13 DOI: 10.1007/s00018-025-05833-3

Feilin Qu, Wei Jian, Yixiang Huang, Xiqian Zhou, Xuehui Wang, JunJie Li, Gang Wang, Mainly

{"title":"Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation.","authors":"Feilin Qu, Wei Jian, Yixiang Huang, Xiqian Zhou, Xuehui Wang, JunJie Li, Gang Wang, Mainly","doi":"10.1007/s00018-025-05833-3","DOIUrl":"10.1007/s00018-025-05833-3","url":null,"abstract":"Background: Triple-negative breast cancer (TNBC) is an aggressive malignancy lacking effective targeted therapies. Given the growing importance of regulated cell death pathways, we investigated the role of USP33 and its interaction with the tumor suppressor TAP63 in modulating ferroptosis and autophagy in TNBC.Methods: An integrative approach combining bioinformatic screening, in vitro molecular and cellular assays, and in vivo xenograft models was employed to evaluate the USP33-TAP63 axis. Protein interaction and ubiquitination were assessed via co-immunoprecipitation and ubiquitin chain analysis. Ferroptosis and autophagy were monitored using fluorescence probes, electron microscopy, and key biomarkers. Statistical significance was assessed via Student's t-test and ANOVA.Results: USP33 was significantly downregulated in TNBC tissues and cell lines, correlating with enhanced proliferation, migration, and epithelial-mesenchymal transition. Mechanistically, USP33 stabilized TAP63 through K48-linked deubiquitination, triggering autophagy and ferroptosis by disrupting mitochondrial function and redox balance. Co-overexpression of USP33 and TAP63 synergistically suppressed tumor growth in vitro and in vivo.Conclusion: The USP33-TAP63 axis acts as a central regulator of autophagy and ferroptosis in TNBC, suppressing tumor progression via oxidative stress-induced cell death. These findings offer mechanistic insight and highlight this axis as a promising target for therapeutic intervention in TNBC.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"309"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834217","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

PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia. PGC1α调节线粒体对循环拉伸的代谢反应，抑制新生内膜增生。

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-08-08 DOI: 10.1007/s00018-025-05790-x

Minwen Zou, Kaichuang Ye, Jing Yan, Shoumin Zhang, Han Bao, Zhiyin Li, Yuting Tao, Xing Zhang, Wenhao Tian, Yingxin Qi, Yunlong Huo, Yue Han

{"title":"PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia.","authors":"Minwen Zou, Kaichuang Ye, Jing Yan, Shoumin Zhang, Han Bao, Zhiyin Li, Yuting Tao, Xing Zhang, Wenhao Tian, Yingxin Qi, Yunlong Huo, Yue Han","doi":"10.1007/s00018-025-05790-x","DOIUrl":"10.1007/s00018-025-05790-x","url":null,"abstract":"Neointimal hyperplasia occurs in the context of vascular injury, such as stent intervention or balloon angioplasty. However, the role of mechanical forces in this process remains to be studied. In this study, a rat carotid artery intimal injury model was established. RNA-sequencing and transmission electron microscopy revealed that intimal injury disrupted the balance of vascular energy metabolism and impaired the mitochondrial ultrastructure in vivo. The human carotid plaque and femoral artery plaque samples also exhibited alterations in mitochondrial morphology. Vascular smooth muscle cells (VSMCs) are the main components of neointimal hyperplasia and are subjected to cyclic stretch resulting from pulsatile pressure. In this study, we found that the application of cyclic stretch in vitro increased VSMC mitochondrial mass and function. In addition, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) played an important role in regulating VSMC mitochondrial function in response to physiological stretch via the phosphorylation of Smad3. Increasing the activation of PGC1α by ZLN005 treatment effectively inhibited VSMC hyperproliferation after intimal injury in vivo. These results suggested that the regulation of PGC1α by p-Smad3 in response to physiological cyclic stretch may effectively alleviate neointimal hyperplasia by promoting mitochondrial function. PGC1α may be a potential therapeutic target for the prevention and treatment of neointimal hyperplasia.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"303"},"PeriodicalIF":6.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798282","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