Cellular & Molecular Biology Letters最新文献

{"title":"Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.","authors":"Ketsia Bakambamba, Manon Nivet, Sophie Martin, Elodie Lafont, Eric Chevet, Tony Avril","doi":"10.1186/s11658-026-00932-w","DOIUrl":"10.1186/s11658-026-00932-w","url":null,"abstract":"<p><p>The eukaryotic secretory pathway (SP) is essential to ensure cellular functions and multicellular communication. The early SP is constituted mostly of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC), and the Golgi apparatus. These intracellular organelles achieve proper folding and modification of newly synthesized transmembrane and secretory proteins, en route to their final destination, e.g., plasma membrane, endosomes, lysosomes, and the extracellular space. They also integrate quality control systems to ensure export of productively folded proteins and to trigger dysfunctional proteins to degradation. The ER as the first SP compartment is subjected to a precise control of its own homeostasis through signaling of the unfolded protein response. In this review, we provide an overview of the early SP and its regulatory mechanisms, focusing on the ER and Golgi stress-dependent signaling. We contextualize this information within physiological and pathological processes, and discuss how ER and Golgi stress responses might coordinate their regulatory effects across the entire SP.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13359550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR and compound screens in a novel ex vivo tissue model identify DDR1 and ETA as regulators of cancer cell invasion.","authors":"Junnan Liu, Wencheng Jiang, Xue Wang, Anca Azoitei, Hengchuan Liu, Gregoire Najjar, Kuangzheng Liu, Michael Karl Melzer, Stephan Stilgenbauer, Mohamed Elati, Martin D Burkhalter, Melanie Philipp, Felix Wezel, Friedemann Zengerling, Christian Bolenz, Cagatay Günes","doi":"10.1186/s11658-026-00936-6","DOIUrl":"10.1186/s11658-026-00936-6","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BC) can be characterized clinically as either non-muscle-invasive (NMIBC) or muscle-invasive (MIBC). While NMIBC generally has a favorable prognosis, MIBC is characterized by high morbidity and mortality. Understanding the molecular determinants of tumor invasion is critical, yet research is hampered by the limitations of current experimental models. Standard assays such as the Boyden chamber lack physiological complexity, while porcine bladder models suffer from tissue contamination and genetic variability. There is an urgent need for reliable models that mimic the intact tissue architecture.</p><p><strong>Methods: </strong>We established a unique ex vivo tissue invasion model (EXTIM) to evaluate the invasive capacity of BC cells within a largely intact tissue context, using freshly prepared bladders from mice. The invasiveness of human BC cells (RT4, T24, UMUC3) and the immortal urothelial cell strain (Y235T) was comparably evaluated using EXTIM, the Boyden chamber, and porcine models. Gene knockdown or ectopic expression of GJB3 or ORP3 indicated the suitability of EXTIM to investigate the impact of specific factors on tumor cell invasion. To identify novel genetic regulators of cell invasion, we combined EXTIM with a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout screen. Additionally, we utilized the EXTIM to perform a pharmacological screen of a small molecule library comprising 90 substances to identify compounds capable of suppressing BC cell dissemination.</p><p><strong>Results: </strong>Importantly, by combining EXTIM with genomewide CRISPR-Cas9 screening, we identified several candidate genes involved in BC progression. Notably, discoidin domain receptor tyrosine kinase 1 (DDR1) was identified as a functional inhibitor of tumor cell invasion. Furthermore, the small-molecule screen revealed that PD-156707, a selective antagonist of the endothelin receptor A (ETA), significantly suppresses cancer cell invasion within the EXTIM environment.</p><p><strong>Conclusions: </strong>EXTIM serves as a robust and physiologically relevant tool for assessing tumor cell invasion and migration under ex vivo conditions. EXTIM can be used to identify factors involved in the progression of invasive BC by high-throughput genetic screenings in an ex vivo organ culture system, by culturing cells after transmigration through the bladder tissue. Moreover, the impact of specific genetic factors in the process of tumor cell dissemination can be assessed by placing bladders from genetically modified mice into the EXTIM.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13277066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNASE1L3 functions as a significant metastatic suppressor by attenuating MYH9/β-catenin/c-Jun/LncRNA-KDM4A-induced E-cadherin ubiquitination degradation in nasopharyngeal carcinoma.","authors":"Xingyu Tao, Xiong Liu, Xiangdong Zhao, Beixian Zhou, Chao Cheng, Weiwei Yan, Jingjing He, Haolin Cao, Yun Su, Jianyang Xin, Xiaoning Gan, Hong Peng, Wanli Lin, Weiyi Fang, Zhen Liu","doi":"10.1186/s11658-026-00911-1","DOIUrl":"10.1186/s11658-026-00911-1","url":null,"abstract":"<p><strong>Background: </strong>Deoxyribonuclease 1 Like 3 (DNASE1L3) is a member of the deoxyribonuclease I family that is associated with some diseases, including systemic lupus erythematosus and hypocomplementemic urticarial vasculitis. Recently, abnormal DNASE1L3 was preliminarily shown to correlate with tumor pathogenesis. However, its role is still undetermined in nasopharyngeal carcinoma (NPC).</p><p><strong>Methods: </strong>Multiple sets of Gene Expression Omnibus (GEO) high-throughput data were utilized to screen the differentially expressed genes. Signal pathway enrichment analysis analyzed the correlation between DNASE1L3 and epithelial-mesenchymal transition (EMT) and cytoskeleton reorganization. An immunohistochemistry assay for analysis of DNASE1L3 expression was used to detect the clinical samples. Woundhealing, migration, invasion assays, and mouse model of lung metastasis were used to assess the role of DNASE1L3 in NPC metastasis. The mechanism of DNASE1L3 inhibition of NPC metastasis by attenuating MYH9/β-catenin/c-Jun/LncRNA-KDM4A-induced E-cadherin ubiquitination degradation was demonstrated by protein stability evaluation, co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation, dual-luciferase reporter assay, and RNA immunoprecipitation.</p><p><strong>Results: </strong>DNASE1L3 downregulation in patients with NPC was not only negatively related to lymph node metastasis and distant metastasis but was also positively associated with poor prognosis. Overexpression of DNASE1L3 in NPC cells suppresses migration, invasion, and metastasis in vitro and in vivo. Inversely, DNASE1L3 knockdown increased cell migration and invasion abilities. Mechanistically, DNASE1L3 recruited PARK2 to ubiquitinate and degrade MYH9 protein. MYH9 protein activated β-catenin/c-Jun signal and augmented c-Jun-induced LncRNA-KDM4A transcription. In the process of DNASE1L3-induced metastatic suppression, decreased LncRNA-KDM4A attenuated the recruitment of E3 ubiquitin ligase Hakai and thus impeded the degradation of E-cadherin, by which heightened E-cadherin protein stability and finally inactivated the EMT signal.</p><p><strong>Conclusions: </strong>Our data firstly elucidated that DNASE1L3 acts as a metastatic suppressor by attenuating E-cadherin ubiquitination degradation via the MYH9/β-catenin/c-Jun/LncRNA-KDM4A axis in NPC. DNASE1L3 is a potential marker for predicting NPC prognosis.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13359980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.","authors":"Jia-Ming Wang, Feng-Hao Zhang, Yi-Ru Chen, Dan-Ni Chen, Xiao Wang, Hai-Yun Xie, Jiang-Feng Li, Jin-Dan Luo, Li-Ping Xie","doi":"10.1186/s11658-026-00909-9","DOIUrl":"10.1186/s11658-026-00909-9","url":null,"abstract":"<p><p>Serotonin, also known as 5-HT, is a classical neurotransmitter produced both in the nervous system and in non-nervous system. Its involvement in various fundamental physiological processes and pathogenic conditions is significant, as it binds to a diverse array of functionally distinct receptors. Apart from binding to 5-HT receptors and activating downstream signaling cascades, recent studies have revealed a novel posttranslational modification named serotonylation, where serotonin is re-taken up by serotonin transporter and is covalently attached to target proteins ranging from histone proteins to nonhistone proteins. Transglutaminases (TGMs), especially TGM2, catalyze serotonylation through the transfer of serotonin to the glutamine residues of target proteins. This review aims to investigate recent progresses in understanding the involvement of serotonylation in physiological and pathological processes. In addition, this review emphasizes how to target serotonylation as a therapeutic strategy for disease management.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.","authors":"Suyakarn Archasappawat, Juliette Jacques, EunJung Lee, Chang-Il Hwang","doi":"10.1186/s11658-026-00922-y","DOIUrl":"10.1186/s11658-026-00922-y","url":null,"abstract":"<p><p>Bromodomain and extraterminal motif (BET) inhibitors, such as JQ1, are promising cancer therapeutics that target epigenetic regulators, particularly BRD4. However, resistance to BET inhibitors (BETi) limits their clinical utility, necessitating a better understanding of adaptive mechanisms. We identified BRD2 upregulation as a conserved response to BET inhibition across multiple cancer types and hypothesized that BRD2 compensates for BRD4 loss, sustaining essential transcriptional programs upon treatment. Consistent with this, BRD2 knockdown sensitized cancer cells to BETi in vitro, and combining BRD2 depletion and JQ1 treatment significantly impaired tumor growth in vivo. At the chromatin level, BRD2 and BRD4 ChIP-seq analysis of pancreatic cancer cells showed consistent BRD4 loss from chromatin after JQ1 treatment, while BRD2 displacement differed by sensitivity. Resistant cells maintained higher BRD2 occupancy than sensitive cells, suggesting a link between BRD2 retention and drug response. Mechanistically, NFYA mediates BRD2 upregulation as NFYA depletion attenuated BRD2 upregulation upon BETi treatment. Collectively, our findings establish BRD2 as a critical mediator of pan-cancer adaptive resistance to BETi and identify NFYA as a novel transcriptional regulator of this process. Co-targeting BRD2 or its regulatory network offers a rational strategy to enhance the durability and efficacy of BET-based therapies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13362212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.","authors":"Chen Lenchisky, Areen Muhammad Majadly, Irena Bronshtein Berger, Danielle Biton, Alaa Daoud Sarsour, Narkis Arbeli, Tamar Cohen, Naama Amos, Sara Kinstlinger, Ortal Cohen, Elad Horwitz, Moran Dvela-Levitt","doi":"10.1186/s11658-026-00931-x","DOIUrl":"10.1186/s11658-026-00931-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The endoplasmic reticulum (ER) plays a central role in protein homeostasis by facilitating the folding, modification, and quality control of secretory and membrane proteins. Disruption of ER function results in protein misfolding and ER stress, which activate the unfolded protein response (UPR). While the three canonical UPR branches, inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6), have been extensively studied, the mechanisms that coordinate their activities and ultimately dictate survival or death remain poorly understood. Transmembrane P24 trafficking protein 9 (TMED9), a cargo receptor that cycles between the ER and Golgi, has been implicated in protein quality control under pathological conditions, but its physiological role in ER proteostasis and UPR signaling is unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The ER stress response was studied in cellular human models including normal epithelial cells and patient-derived pediatric glioma cultures. To define the regulatory mechanisms dictating TMED9 expression, quantitative Reverse Transcription polymerase chain reaction (qRT-PCR), luciferase reporter assay, and western blotting were employed. To elucidate TMED9 function, loss-of-function approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated knockout and small interfering RNA knockdown were used in combination with RNA-seq and live imaging. Protein stability was tested by pulse-chase experiments, ubiquitination, and degradation analyses. To study the implications of TMED9 activation, we screened curated gene expression datasets from the European Molecular Biology Laboratory- European Bioinformatics Institute (EMBL-EBI) Expression Atlas and employed live-cell imaging-based assays and functional assays (cell viability, apoptosis, migration, and self-renewal).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our study uncovers a physiological role for TMED9 in ER proteostasis and UPR signaling. We show that, under ER stress, TMED9 expression is transcriptionally induced by the IRE1-spliced X-box binding protein 1 (XBP1s) pathway via a conserved unfolded protein response element (UPRE)-like element in its promoter. Removal of TMED9 selectively impairs ATF6 activation without altering IRE1 or PERK signaling, resulting in increased sensitivity to ER stress-induced apoptosis. Mechanistically, we identify TMED9 as a stress-induced stabilizer of ATF6 that prevents its ubiquitin-dependent proteasomal degradation. Functionally, TMED9 regulation is exploited by tumor cells, which sustain IRE1-XBP1s activity to upregulate TMED9, thereby enhancing survival under ER stress conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Collectively, our findings establish TMED9 as a critical regulator of ER stress adaptation. TMED9 emerges as a molecular mediator that links IRE1-dependent transcriptional response to ATF6 ","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentiation state affects PD-L1 expression in cutaneous melanoma: a systematic review.","authors":"Teitur Sævarsson, Hong Nhung Vu, Eiríkur Steingrímsson, Berglind Ósk Einarsdóttir","doi":"10.1186/s11658-026-00934-8","DOIUrl":"10.1186/s11658-026-00934-8","url":null,"abstract":"<p><strong>Background: </strong>Programmed death ligand-1 (PD-L1) is a widely used biomarker for immunotherapy in melanoma. The expression of PD-L1 in melanoma cells is known to vary considerably among and within patients' tumor samples. Recent studies suggest that there may be a link between PD-L1 expression and the differentiation status of melanoma cells which is known to fluctuate in response to external stimuli and to be influenced by a multitude of regulators. Here, we systematically review which differentiation regulators affect PD-L1 expression in melanoma.</p><p><strong>Methods: </strong>A systematic review was performed on studies collected through PubMed, Scopus, and Web of Knowledge up until February 13^th, 2026. Screening of abstracts and titles was performed independently by two reviewers. Screening of full-text articles, data extraction, and validity assessments were performed by one reviewer. Studies published in English reporting changes in PD-L1 expression associated with a known differentiation regulator in a melanocytic/melanoma model were included. Studies were assessed for risk of bias regarding imprecision in experimental reporting and model validity, using previously defined assessment tools. Synthesis of results was performed narratively.</p><p><strong>Results: </strong>Out of 496 identified articles, 57 studies met the inclusion criteria. A total of 16 differentiation regulators were significantly associated with PD-L1 expression in melanoma cells. Most studies (45/57) reported a single regulator, while 12/57 reported multiple. STAT3 appeared in 20/57 studies; all other regulators were reported in eight or fewer. PD-L1 expression was positively associated with all dedifferentiation-linked regulators (9/9). Among differentiation-linked regulators, 3/4 (MITF, SOX10, IRF4) showed contrasting associations depending on the PD-L1 expression mode and study. In total, 120 human and 10 mouse melanoma cell lines were used. The A375, SK-MEL-28, and B16 cell lines were used in 20, 18, and 28 studies, respectively, suggesting lineage bias. Most studies had unclear risk of bias regarding imprecision (82%) and model validity (70%).</p><p><strong>Conclusions: </strong>PD-L1 expression is commonly affected by differentiation regulators in melanoma cells, linking high PD-L1 expression to dedifferentiated cell states. The various regulators and inducible pathways that affect PD-L1 may in turn explain the heterogeneity observed in PD-L1 expression between and within patients with melanoma. Owing to the clinical significance of PD-L1 expression as a predictive biomarker for immunotherapy response, it is crucial to better understand the impact of various regulators on its expression.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chicoric acid targets PYGL to normalize glycogenolysis-driven glycolysis to suppress non-small cell lung cancer.","authors":"Xingfa Huo, Helei Hou, Chuantao Zhang, Xueqin Duan, Hongwei Lan, Yufeng Li, Na Zhou, Xiaochun Zhang","doi":"10.1186/s11658-026-00930-y","DOIUrl":"10.1186/s11658-026-00930-y","url":null,"abstract":"<p><strong>Background: </strong>Chicoric acid (CA), a bioactive natural compound found in Chicory and Echinacea purpurea, exhibits antiinflammatory, antioxidant, and apoptosis-inducing properties. However, its therapeutic potential and underlying mechanisms in non-small cell lung cancer (NSCLC) remain unclear.</p><p><strong>Methods: </strong>We utilized bioinformatics analysis to identify potential hub genes targeted by CA. The clinical relevance of glycogen phosphorylase liver form (PYGL) was assessed via immunohistochemistry in NSCLC tissues. Functional assays, including Cell Counting Kit-8, flow cytometry, and xenograft models, were employed to evaluate the impact of PYGL on tumor growth. Glycogen metabolism and glycolytic flux were monitored using PAS staining and Seahorse assays. Direct binding between CA and PYGL was confirmed through virtual screening, molecular docking, cellular thermal shift assay, and surface plasmon resonance. Binding specificity was further validated using site-directed mutagenesis.</p><p><strong>Results: </strong>Here, we demonstrate that CA restores glucose metabolic homeostasis and inhibits the proliferation of NSCLC cells. We identified PYGL as a key driver of NSCLC, where its upregulation enhances glycogenolysis to fuel glycolytic flux and promote tumor growth. Mechanistically, CA allosterically inhibits PYGL by binding to specific residues (Glu162, Arg247, Glu273) and inducing conformational changes, thereby suppressing glycogenolysis and reducing glycolysis. Furthermore, CA disrupts the interaction between PYGL and lactate dehydrogenase A (LDHA), accelerating the proteasomal degradation of LDHA and further reshaping glucose metabolic homeostasis.</p><p><strong>Conclusions: </strong>Our findings highlight PYGL as a metabolic vulnerability in NSCLC and establish CA as a promising lead compound that targets the PYGL-LDHA axis to reprogram glucose metabolism and inhibit tumor growth.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental exosomal miR-372-3p drives preeclampsia progression by inducing mitochondrial damage in RVLM neurons.","authors":"Shuai Zhang, Linping Wang, Bingjie Zhao, Tengteng Dai, Maolin Nie, Lei Tong, Qiangcheng Zeng, Wei Guo, Yongmei Shen, Dongshu Du","doi":"10.1186/s11658-026-00929-5","DOIUrl":"10.1186/s11658-026-00929-5","url":null,"abstract":"<p><p>BACKGROUND: Preeclampsia (PE) is a pregnancy-specific disorder rooted in placental dysfunction, characterized by new-onset hypertension with proteinuria and/or end-organ dysfunction, often linked to sympathetic overactivation. The rostral ventrolateral medulla (RVLM) serves as a crucial hub for sympathetic and blood pressure (BP) control. Placental exosomes are implicated in PE, but their role in placenta–RVLM communication is unclear. Investigating this could reveal the neurogenic pathogenesis underlying cardiovascular dysregulation in PE. METHODS: Placental exosomes derived from patients with PE (PE-exo) and normal pregnancies (N-exo) were isolated by ultracentrifugation. Their roles in regulating RVLM neuronal excitability, sympathetic tone, and BP, along with the underlying mechanisms, were evaluated using various experiments. RESULTS: Tail vein injection of PE-exo significantly enhanced RVLM neuronal excitability, sympathetic tone, and BP in pregnant rats. miR-372-3p levels were significantly elevated in PE-exo compared with N-exo and were upregulated in the RVLM of pregnant rats following PE-exo administration. miR-372-3p knockdown reversed the PE-exo-induced increases in RVLM neuronal excitability, sympathetic tone, and BP in pregnant rats. Mechanistically, miR-372-3p markedly reduced MPC1 expression, leading to RVLM neuronal mitochondrial damage. CONCLUSIONS: This study is the first to demonstrate that placental exosomes deliver miR-372-3p to the RVLM neurons, impairing neuronal mitochondrial function and thereby promoting neuronal hyperexcitability, sympathetic overactivity, and elevated BP in PE. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulated CCN1 from pleural mesothelial cells alters collagen I conformation and drives fibrosis via ITGB1/MAPK signaling.","authors":"Xiao-Lin Cui, Lin-Jie Song, Qian Li, Zi-Heng Jia, Xiyong Dai, Meng Wang, Yang-Ping Lv, Shuai-Jun Chen, He-De Zhang, Pei-Pei Cheng, Shu-Yi Ye, Shi-He Hu, Chen-Yue Lian, Li-Mei Liang, Fan Yu, Xin-Liang He, Liang Xiong, Fei Xiang, Xiaorong Wang, Hong Ye, Wan-Li Ma","doi":"10.1186/s11658-026-00928-6","DOIUrl":"10.1186/s11658-026-00928-6","url":null,"abstract":"<p><p>BACKGROUND: Pleural mesothelial cells (PMCs) have been identified as key contributors to pleural fibrosis. Cellular communication network factor 1 (CCN1), a matricellular protein, regulates cell–matrix interactions and fibrotic signaling in multiple contexts. However, the specific role and mechanism of CCN1 in PMCs during pleural fibrosis remained unclear. METHODS: Expression of CCN1 was evaluated in human pleural fibrosis samples and bleomycin-induced mouse models. In vitro, PMCs were treated with recombinant CCN1 or fibrotic matrix. Mechanistic studies included gene knockdown, immunoprecipitation, mass spectrometry, and functional assays. RESULTS: CCN1 was significantly elevated in pleural fibrosis tissues. CCN1 expression was driven by YAP/TAZ activation and in turn promoted further YAP/TAZ activation, creating a feedback loop to produce more CCN1. Upregulated CCN1 directly altered conformation of type I collagen (collagen I) by binding vWC binding domain. Then, CCN1 with conformation-changed collagen I activated integrin β1 (ITGB1)/MAPK signaling, which induced remodeling of cytoskeleton as well as fibrosis. At last, it was confirmed that neutralization of CCN1 reduced pleural fibrosis in vitro and in vivo. CONCLUSIONS: Upregulated CCN1 contributes to pleural fibrosis via changing collagen I conformation and ITGB1/MAPK pathway activation. Targeting CCN1 is a potential therapeutic strategy. </p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":12.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}