Cells最新文献_第2页

YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis 肺纤维化病理生物学中的 YAP/TAZ 信号传导

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181519

Kostas A. Papavassiliou, Amalia A. Sofianidi, Fotios G. Spiliopoulos, Vassiliki A. Gogou, Antonios N. Gargalionis, Athanasios G. Papavassiliou

{"title":"YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis","authors":"Kostas A. Papavassiliou, Amalia A. Sofianidi, Fotios G. Spiliopoulos, Vassiliki A. Gogou, Antonios N. Gargalionis, Athanasios G. Papavassiliou","doi":"10.3390/cells13181519","DOIUrl":"https://doi.org/10.3390/cells13181519","url":null,"abstract":"Pulmonary fibrosis (PF) is a severe, irreversible lung disease characterized by progressive scarring, with idiopathic pulmonary fibrosis (IPF) being the most prevalent form. IPF’s pathogenesis involves repetitive lung epithelial injury leading to fibroblast activation and excessive extracellular matrix (ECM) deposition. The prognosis for IPF is poor, with limited therapeutic options like nintedanib and pirfenidone offering only modest benefits. Emerging research highlights the dysregulation of the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway as a critical factor in PF. YAP and TAZ, components of the Hippo pathway, play significant roles in cell proliferation, differentiation, and fibrosis by modulating gene expression through interactions with TEA domain (TEAD) transcription factors. The aberrant activation of YAP/TAZ in lung tissue promotes fibroblast activation and ECM accumulation. Targeting the YAP/TAZ pathway offers a promising therapeutic avenue. Preclinical studies have identified potential treatments, such as trigonelline, dopamine receptor D1 (DRD1) agonists, and statins, which inhibit YAP/TAZ activity and demonstrate antifibrotic effects. These findings underscore the importance of YAP/TAZ in PF pathogenesis and the potential of novel therapies aimed at this pathway, suggesting a new direction for improving IPF treatment outcomes. Further research is needed to validate these approaches and translate them into clinical practice.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199687","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

The Oncoprotein Fra-2 Drives the Activation of Human Endogenous Retrovirus Env Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) Patients 肿瘤蛋白Fra-2驱动成人T细胞白血病/淋巴瘤（ALLL）患者体内人类内源性逆转录病毒Env表达的激活

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181517

Julie Tram, Laetitia Marty, Célima Mourouvin, Magali Abrantes, Ilham Jaafari, Raymond Césaire, Philippe Hélias, Benoit Barbeau, Jean-Michel Mesnard, Véronique Baccini, Laurent Chaloin, Jean-Marie Jr. Peloponese

{"title":"The Oncoprotein Fra-2 Drives the Activation of Human Endogenous Retrovirus Env Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) Patients","authors":"Julie Tram, Laetitia Marty, Célima Mourouvin, Magali Abrantes, Ilham Jaafari, Raymond Césaire, Philippe Hélias, Benoit Barbeau, Jean-Michel Mesnard, Véronique Baccini, Laurent Chaloin, Jean-Marie Jr. Peloponese","doi":"10.3390/cells13181517","DOIUrl":"https://doi.org/10.3390/cells13181517","url":null,"abstract":"Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs’ aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8+-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199685","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

Dynamic Mitotic Localization of the Centrosomal Kinases CDK1, Plk, AurK, and Nek2 in Dictyostelium amoebae 变形虫中中心体激酶 CDK1、Plk、AurK 和 Nek2 的动态有丝分裂定位

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181513

Stefan Krüger, Nathalie Pfaff, Ralph Gräf, Irene Meyer

引用次数: 0

Small Extracellular Vesicles and Oral Mucosa: The Power Couple in Regenerative Therapies? 细胞外小泡和口腔黏膜：再生疗法中的强强联手？

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181514

Blanka Maria Borowiec, Marta Dyszkiewicz-Konwińska, Dorota Bukowska, Michał Nowicki, Joanna Budna-Tukan

{"title":"Small Extracellular Vesicles and Oral Mucosa: The Power Couple in Regenerative Therapies?","authors":"Blanka Maria Borowiec, Marta Dyszkiewicz-Konwińska, Dorota Bukowska, Michał Nowicki, Joanna Budna-Tukan","doi":"10.3390/cells13181514","DOIUrl":"https://doi.org/10.3390/cells13181514","url":null,"abstract":"Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, new methods in regenerative medicine are continually sought, and existing ones are being improved. Small extracellular vesicles (sEVs) have gained attention for their regenerative potential, as evidenced by existing studies conducted by independent research groups. Of particular interest are sEVs derived from the oral mucosa, a tissue renowned for its rapid regeneration and minimal scarring. While the individual regenerative potential of both sEVs and the oral mucosa is somewhat understood, the combined potential of sEVs derived from the oral mucosa has not been sufficiently explored and highlighted in the existing literature. Serving as a broad compendium, it aims to provide scientists with essential and detailed information on this subject, including the nature of the materials employed, isolation and analysis methodologies, and clinical applications. The content of this survey aims to facilitate the comparison of diverse methods for working with sEVs derived from the oral mucosa, aiding in the planning of research endeavors and identifying potential research gaps.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199683","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

FGF23 and Cell Stress in SaOS-2 Cells—A Model Reflecting X-Linked Hypophosphatemia Dynamics FGF23与SaOS-2细胞中的细胞应激--反映X-遗传性低磷血症动态的模型

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181515

Lisanne Brueck, Sascha Roocke, Veronika Matschke, Annette Richter-Unruh, Katrin Marcus-Alic, Carsten Theiss, Sarah Stahlke

{"title":"FGF23 and Cell Stress in SaOS-2 Cells—A Model Reflecting X-Linked Hypophosphatemia Dynamics","authors":"Lisanne Brueck, Sascha Roocke, Veronika Matschke, Annette Richter-Unruh, Katrin Marcus-Alic, Carsten Theiss, Sarah Stahlke","doi":"10.3390/cells13181515","DOIUrl":"https://doi.org/10.3390/cells13181515","url":null,"abstract":"Our study investigates the impact of FGF23 overexpression on SaOS-2 cells to elucidate its role in cellular stress and morphology, contributing to the understanding of skeletal pathologies like X-linked hypophosphatemia (XLH). Using transmission electron microscopy and protein analysis (Western blot), we analyzed the rough endoplasmic reticulum (rER) and mitochondria in SaOS-2 cells with FGF23 overexpression compared to controls. We found significant morphological changes, including enlarged and elongated rER and mitochondria, with increased contact zones, suggesting enhanced interaction and adaptation to elevated protein synthesis and secretion demands. Additionally, we observed higher apoptosis rates of the cells after 24–72 h in vitro and upregulated proteins associated with ER stress and apoptosis, such as CHOP, XBP1 (spliced and unspliced), GRP94, eIF2α, and BAX. These findings indicate a robust activation of the unfolded protein response (UPR) and apoptotic pathways due to FGF23 overexpression. Our results highlight the critical role of ER and mitochondrial interactions in cellular stress responses and provide new insights into the mechanistic link between FGF23 signaling and cellular homeostasis. In conclusion, our study underscores the importance of analyzing UPR-related pathways in the development of therapeutic strategies for skeletal and systemic diseases and contributes to a broader understanding of diseases like XLH.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225799","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

Postencephalitic Parkinsonism: Unique Pathological and Clinical Features—Preliminary Data 脑后帕金森病：独特的病理和临床特征--初步数据

IF 6 2区生物学

Cells Pub Date : 2024-09-10 DOI: 10.3390/cells13181511

Sabrina Strobel, Jeswinder Sian-Hulsmann, Dennis Tappe, Kurt Jellinger, Peter Riederer, Camelia-Maria Monoranu

{"title":"Postencephalitic Parkinsonism: Unique Pathological and Clinical Features—Preliminary Data","authors":"Sabrina Strobel, Jeswinder Sian-Hulsmann, Dennis Tappe, Kurt Jellinger, Peter Riederer, Camelia-Maria Monoranu","doi":"10.3390/cells13181511","DOIUrl":"https://doi.org/10.3390/cells13181511","url":null,"abstract":"Postencephalitic parkinsonism (PEP) is suggested to show a virus-induced pathology, which is different from classical idiopathic Parkinson’s disease (PD) as there is no α-synuclein/Lewy body pathology. However, PEP shows a typical clinical representation of motor disturbances. In addition, compared to PD, there is no iron-induced pathology. The aim of this preliminary study was to compare PEP with PD regarding iron-induced pathology, using histochemistry methods on paraffin-embedded post-mortem brain tissue. In the PEP group, iron was not seen, except for one case with sparse perivascular depositions. Rather, PEP offers a pathology related to tau-protein/neurofibrillary tangles, with mild to moderate memory deficits only. It is assumed that this virus-induced pathology is due to immunological dysfunctions causing (neuro)inflammation-induced neuronal network disturbances as events that trigger clinical parkinsonism. The absence of iron deposits implies that PEP cannot be treated with iron chelators. The therapy with L-Dopa is also not an option, as L-Dopa only leads to an initial slight improvement in symptoms in isolated cases.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199665","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

Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS 针对 NAD+ 代谢的 ALS 潜在治疗干预措施

IF 6 2区生物学

Cells Pub Date : 2024-09-09 DOI: 10.3390/cells13171509

Samuel Lundt, Shinghua Ding

{"title":"Potential Therapeutic Interventions Targeting NAD+ Metabolism for ALS","authors":"Samuel Lundt, Shinghua Ding","doi":"10.3390/cells13171509","DOIUrl":"https://doi.org/10.3390/cells13171509","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. While there have been many potential factors implicated for ALS development, such as oxidative stress and mitochondrial dysfunction, no exact mechanism has been determined at this time. Nicotinamide adenine dinucleotide (NAD+) is one of the most abundant metabolites in mammalian cells and is crucial for a broad range of cellular functions from DNA repair to energy homeostasis. NAD+ can be synthesized from three different intracellular pathways, but it is the NAD+ salvage pathway that generates the largest proportion of NAD+. Impaired NAD+ homeostasis has been connected to aging and neurodegenerative disease-related dysfunctions. In ALS mice, NAD+ homeostasis is potentially disrupted prior to the appearance of physical symptoms and is significantly reduced in the nervous system at the end stage. Treatments targeting NAD+ metabolism, either by administering NAD+ precursor metabolites or small molecules that alter NAD+-dependent enzyme activity, have shown strong beneficial effects in ALS disease models. Here, we review the therapeutic interventions targeting NAD+ metabolism for ALS and their effects on the most prominent pathological aspects of ALS in animal and cell models.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199613","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

Class Effect Unveiled: PPARγ Agonists and MEK Inhibitors in Cancer Cell Differentiation 类效应揭开面纱：PPARγ 激动剂和 MEK 抑制剂在癌细胞分化中的作用

IF 6 2区生物学

Cells Pub Date : 2024-09-09 DOI: 10.3390/cells13171506

Rakefet Ben-Yishay, Opher Globus, Nora Balint-Lahat, Sheli Arbili-Yarhi, Neta Bar-Hai, Vered Bar, Sara Aharon, Anna Kosenko, Adi Zundelevich, Raanan Berger, Dana Ishay-Ronen

{"title":"Class Effect Unveiled: PPARγ Agonists and MEK Inhibitors in Cancer Cell Differentiation","authors":"Rakefet Ben-Yishay, Opher Globus, Nora Balint-Lahat, Sheli Arbili-Yarhi, Neta Bar-Hai, Vered Bar, Sara Aharon, Anna Kosenko, Adi Zundelevich, Raanan Berger, Dana Ishay-Ronen","doi":"10.3390/cells13171506","DOIUrl":"https://doi.org/10.3390/cells13171506","url":null,"abstract":"Epithelial-to-mesenchymal transition (EMT) plays a major role in breast cancer progression and the development of drug resistance. We have previously demonstrated a trans-differentiation therapeutic approach targeting invasive dedifferentiated cancer cells. Using a combination of PPARγ agonists and MEK inhibitors, we forced the differentiation of disseminating breast cancer cells into post-mitotic adipocytes. Utilizing murine breast cancer cells, we demonstrated a broad class effect of PPARγ agonists and MEK inhibitors in inducing cancer cell trans-differentiation into adipocytes. Both Rosiglitazone and Pioglitazone effectively induced adipogenesis in cancer cells, marked by PPARγ and C/EBPα upregulation, cytoskeleton rearrangement, and lipid droplet accumulation. All tested MEK inhibitors promoted adipogenesis in the presence of TGFβ, with Cobimetinib showing the most prominent effects. A metastasis ex vivo culture from a patient diagnosed with triple-negative breast cancer demonstrated a synergistic upregulation of PPARγ with the combination of Pioglitazone and Cobimetinib. Our results highlight the potential for new therapeutic strategies targeting cancer cell plasticity and the dedifferentiation phenotype in aggressive breast cancer subtypes. Combining differentiation treatments with standard therapeutic approaches may offer a strategy to overcome drug resistance.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199611","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

Human Endometrial Pericytes: A Comprehensive Overview of Their Physiological Functions and Implications in Uterine Disorders 人类子宫内膜周细胞：子宫内膜周细胞的生理功能及其对子宫疾病的影响综述

IF 6 2区生物学

Cells Pub Date : 2024-09-09 DOI: 10.3390/cells13171510

Yiqun Tang, Caroline Frisendahl, Terhi T. Piltonen, Riikka K. Arffman, Parameswaran Grace Lalitkumar, Kristina Gemzell-Danielsson

引用次数: 0

Functional Insights in PLS3-Mediated Osteogenic Regulation PLS3 介导的成骨调控功能透视

IF 6 2区生物学

Cells Pub Date : 2024-09-09 DOI: 10.3390/cells13171507

Wenchao Zhong, Janine Neugebauer, Janak L. Pathak, Xingyang Li, Gerard Pals, M. Carola Zillikens, Elisabeth M. W. Eekhoff, Nathalie Bravenboer, Qingbin Zhang, Matthias Hammerschmidt, Brunhilde Wirth, Dimitra Micha

{"title":"Functional Insights in PLS3-Mediated Osteogenic Regulation","authors":"Wenchao Zhong, Janine Neugebauer, Janak L. Pathak, Xingyang Li, Gerard Pals, M. Carola Zillikens, Elisabeth M. W. Eekhoff, Nathalie Bravenboer, Qingbin Zhang, Matthias Hammerschmidt, Brunhilde Wirth, Dimitra Micha","doi":"10.3390/cells13171507","DOIUrl":"https://doi.org/10.3390/cells13171507","url":null,"abstract":"Plastin-3 (PLS3) encodes T-plastin, an actin-bundling protein mediating the formation of actin filaments by which numerous cellular processes are regulated. Loss-of-function genetic defects in PLS3 are reported to cause X-linked osteoporosis and childhood-onset fractures. However, the molecular etiology of PLS3 remains elusive. Functional compensation by actin-bundling proteins ACTN1, ACTN4, and FSCN1 was investigated in zebrafish following morpholino-mediated pls3 knockdown. Primary dermal fibroblasts from six patients with a PLS3 variant were also used to examine expression of these proteins during osteogenic differentiation. In addition, Pls3 knockdown in the murine MLO-Y4 cell line was employed to provide insights in global gene expression. Our results showed that ACTN1 and ACTN4 can rescue the skeletal deformities in zebrafish after pls3 knockdown, but this was inadequate for FSCN1. Patients’ fibroblasts showed the same osteogenic transdifferentiation ability as healthy donors. RNA-seq results showed differential expression in Wnt1, Nos1ap, and Myh3 after Pls3 knockdown in MLO-Y4 cells, which were also associated with the Wnt and Th17 cell differentiation pathways. Moreover, WNT2 was significantly increased in patient osteoblast-like cells compared to healthy donors. Altogether, our findings in different bone cell types indicate that the mechanism of PLS3-related pathology extends beyond actin-bundling proteins, implicating broader pathways of bone metabolism.","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142199612","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