Journal of Molecular Medicine-Jmm最新文献

{"title":"CD155 promotes the advancement of hepatocellular carcinoma by suppressing the p53-mediated ferroptosis via interacting with CD96.","authors":"Zhenhui Lu, Jingzhe Yu, Tuoyu Lu, Siyuan Deng, Xuzhen Zheng, Baiyu Ji, Xiangyang Wu, Yingzi Yu","doi":"10.1007/s00109-025-02515-2","DOIUrl":"10.1007/s00109-025-02515-2","url":null,"abstract":"<p><p>This work researched the influence and mechanism of CD155 on hepatocellular carcinoma advancement. CD155 expression and its effect on survival of hepatocellular carcinoma patients were analyzed based on the GEPIA2 database. String software predicted the interacting between CD155 and CD96, which was further verified by co-immunoprecipitation experiment. The function of CD155 and CD96 on the proliferation, migration, and invasion of hepatocellular carcinoma cells (HCC) was explored by colony formation, wound healing, and transwell assays. To research the effect of CD155 and CD96 on ferroptosis, ferroptosis-related factors in HCC were investigated. CD155 and p53 were both silenced in HCC to explore whether CD155 regulates hepatocellular carcinoma progression by acting on p53. Xenograft tumor study was conducted to examine the impact of CD155 on the in vivo growth of HCC. It was discovered that, CD155 up-regulation predicted poor survival of hepatocellular carcinoma patients. CD155 could be interacted with CD96. The proliferation, migration, and invasion of HCC were heightened by CD155. However, ferroptosis was suppressed by CD155, as CD155 decreased p53 and iron but increased SLC7A11, GPX4 and GSH in HCC. In fact, CD96 silencing abolished these effects of CD155. The suppressed malignant behaviors and the enhanced ferroptosis in HCC induced by CD155 silencing were abrogated by p53 silencing. In vivo, CD155 silencing suppressed growth and enhanced ferroptosis of hepatocellular carcinoma, which were counteracted by p53 silencing. Thus, CD155 might facilitate hepatocellular carcinoma advancement through blocking the p53-mediated ferroptosis via interacting with CD96. CD155 might be a promising target for treating hepatocellular carcinoma. KEY MESSAGES: CD155 was up-regulated in hepatocellular carcinoma, predicting poor survival. CD155 protein could be interacted with CD96 protein. Proliferation and invasion of liver cancer cells were facilitated by CD155. Proliferation and invasion of liver cancer cells were decreased by CD96 loss. CD155 promoted liver cancer by suppressing p53-mediated ferroptosis via CD96.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"285-299"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of endosomal RANKL-LGR4 signaling during osteoclast differentiation.","authors":"Beom Chang Kim, Yong Jin Cho, Yuria Jang, Kang Yeol Ko, Chang-Moon Lee, Wonbong Lim","doi":"10.1007/s00109-025-02523-2","DOIUrl":"10.1007/s00109-025-02523-2","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also known as GPR48) is a membrane receptor that negatively regulates the RANK signaling cascade during osteoclastogenesis. Traditionally, cell signaling and endocytic membrane trafficking via membrane receptors have been considered distinct processes; however, they are now recognized to be closely and bidirectionally linked. The present study investigated the difference between membrane-bound and endosomal LGR4 signaling and whether the LGR4 signaling pathway influences RANK-RANKL signaling during RANKL-induced osteoclastogenesis. We used CRISPR-Cas9 to create LGR4 conditional knock-out (CKO) in RAW 264.7 cells and Drg2 knockout (KO) in mice to study the impacts of LGR4 and DRG2 on osteoclastogenesis. LGR4 was endocytosed into endosomes after binding to RANKL in RAW 264.7 s osteoclast precursor cells. Within the early endosomes, internalized LGR4 activates LGR4-RANKL signaling. When bound to RANKL, LGR4 is endocytosed and localized in the RAB5-positive endosomes. In Lgr4 CKO RAW 264.7 cells, early endosome signaling was increased and the inhibitory phosphorylation of GSK-3β was decreased, both in the whole lysate and endosome fraction. RANKL treatment increased nuclear translocation of NFATC1 in Lgr4 CKO RAW 264.7 cells and Drg2 KO mice. Overall, our results suggested that RANKL-LGR4 signaling is regulated by membrane-to-endosomal trafficking during osteoclastogenesis. KEY MESSAGES: Bone resorption by osteoclasts is essential for bone homeostasis and remodeling. However, the mechanisms underlying the regulation of osteoclastogenesis are not yet fully understood. The present study investigated the difference between membrane-bound and endosomal LGR4 signaling, and whether the LGR4 signaling pathway influences RANK-RANKL signaling during RANKL-induced osteoclastogenesis. Our results suggested that RANKL-LGR4 signaling is regulated by membrane-to-endosomal trafficking during osteoclastogenesis.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"339-354"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic insights on abdominal aortic aneurysm and peripheral arterial disease.","authors":"Helena Beatriz Ferreira, Fábio Trindade, Rita Nogueira-Ferreira, Adelino Leite-Moreira, Rita Ferreira, Marina Dias-Neto, M Rosário Domingues","doi":"10.1007/s00109-025-02524-1","DOIUrl":"https://doi.org/10.1007/s00109-025-02524-1","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) and peripheral arterial disease (PAD) are two cardiovascular diseases associated with considerable morbidity, mortality and quality of life impairment. As they are multifactorial diseases, several factors contribute to their pathogenesis, including oxidative stress and lipid peroxidation, and these may have key roles in the development of these pathologies. Alterations of the lipid metabolism and lipid profile have been reported in cardiovascular diseases but to a lesser extent in AAA and PAD. Modifications in the profile of some molecular lipid species, in particular, native phospholipid and triglyceride species were mainly reported for AAA, while alterations in the fatty acid profile were noticed in the case of PAD. Oxidized phospholipids were also reported for AAA. Although AAA and PAD have a common atherosclerotic root, lipidomics demonstrates the existence of distinct lipid. Lipidomic research regarding AAA and PAD is still scarce and should be set in motion to increase the knowledge on the lipid changes that occur in these diseases, contributing not only to the discovery of new biomarkers for diagnosis and prognosis assessment but also to tailor precision medicine in the clinical field.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of circulating glypican 4 as a novel biomarker in disease - A comprehensive review.","authors":"A Muendlein, A Leiherer, H Drexel","doi":"10.1007/s00109-025-02520-5","DOIUrl":"https://doi.org/10.1007/s00109-025-02520-5","url":null,"abstract":"<p><p>Glypican 4 (GPC4), a member of the cell surface heparan sulfate proteoglycan family, plays a crucial role in regulating various cell signaling and developmental processes. Its ability to be released from the cell surface into the bloodstream through shedding makes it a promising blood-based biomarker in health and disease. In this context, circulating GPC4 has been initially proposed as an insulin-sensitizing adipokine being linked with various conditions of insulin resistance. In addition, serum levels of GPC4 can indicate glycocalyx shedding and associated pathophysiological states, such as systemic inflammation. Particularly in a morbid and elderly population, increased GPC4 concentrations may reflect general organ dysfunction and an advanced state of multimorbidity, showing a strong association with the prognosis of severe conditions such as heart failure or advanced cancer. This comprehensive review is the first to summarize the existing scientific knowledge on the role of circulating GPC4 as a novel diagnostic and prognostic biomarker across different pathologic conditions. We also discuss in detail the putative underlying pathophysiological mechanisms behind these findings.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell-derived extracellular vesicles in periodontal bone repair.","authors":"Mengbing Chen, Bo Huang, Xiaoxia Su","doi":"10.1007/s00109-025-02513-4","DOIUrl":"10.1007/s00109-025-02513-4","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease that destroys tooth-supporting structures and poses significant public health challenges due to its high prevalence and links to systemic health conditions. Traditional treatments are effective in reducing the inflammatory response and improving the clinical symptoms of periodontitis. However, these methods are challenging to achieve an ideal treatment effect in alveolar bone repair. Mesenchymal stem cells (MSCs) represent a potential alternative for the treatment of periodontal bone defects due to their self-renewal and differentiation capabilities. Recent research indicates that MSCs exert their effects primarily through paracrine mechanisms. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) serve as pivotal mediators in intercellular communication, transferring microRNAs (miRNAs), messenger RNAs (mRNAs), proteins, and cytokines to recipient cells, thereby emulating the therapeutic effects of MSCs. In periodontitis, MSC-EVs play a pivotal role in immunomodulation and bone remodeling, thereby facilitating periodontal bone repair. As a cell-free therapy, MSC-EVs demonstrate considerable clinical potential due to their specialized membrane structure, minimal immunogenicity, low toxicity, high biocompatibility, and nanoscale size. This review indicates that MSC-EVs represent a promising approach for periodontitis treatment, with the potential to overcome the limitations of traditional therapies and offer a more effective solution for bone repair in periodontal disease. In this review, we introduce MSC-EVs, emphasizing their mechanisms and clinical applications in periodontal bone repair. It synthesizes recent advances, existing challenges, and future prospects to present up-to-date information and novel techniques for periodontal regeneration and to guide the improvement of MSC-EV therapy in clinical practice.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"137-156"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircRNA CDR1AS promotes cardiac ischemia-reperfusion injury in mice by triggering cardiomyocyte autosis.","authors":"Lina Xuan, Jun Chen, Hua Yang, Junwei Hao, Siyun Li, Qingqing Zhang, Hailong Zhang, Shengjie Wang, Huishan Luo, Jianjun Guo, Xingmei Yang, Guangze Wang, Feihan Sun, Xiaolin Hu, Kai Kang, Lihua Sun","doi":"10.1007/s00109-024-02511-y","DOIUrl":"10.1007/s00109-024-02511-y","url":null,"abstract":"<p><p>Myocardial ischemia/reperfusion (IR) injury is a common adverse event in the clinical treatment of myocardial ischemic disease. Autosis is a form of cell death that occurs when autophagy is excessive in cells, and it has been associated with cardiac IR damage. This study aimed to investigate the regulatory mechanism of circRNA CDR1AS on autosis in cardiomyocytes under IR. The expression of CDR1AS increases after myocardial IR, and overexpression of CDR1AS detrimentally affects cardiac function, increases infarct area, promotes excessive autophagy, and blocks the flow of autophagy to induce autosis after IR. Conversely, knockdown of CDR1AS reversed the autophagy-related markers caused by IR, increasing cardiomyocyte activity, improving cardiac dysfunction and infarct area, and restoring the flow of autophagy. Further analysis of RNA sequencing and validation experiments revealed that CDR1AS aggravated autophagic damage, increased autophagosome accumulation, and promoted autosis by inhibiting the levels of LAMP2 and mTORC1 proteins. Additionally, RIP and pull-down assays showed that CDR1AS interacts with LAMP2 or mTORC1. First-time evidence reveals that circRNA CDR1AS regulates lysosomal membrane proteins by regulating the mTORC1/ULK1 pathway during myocardial IR-induced autosis. This suggests that maintaining moderate autophagy is a crucial part of the fight against myocardial IR damage. KEY MESSAGES: CDR1AS expression was significantly increased in myocardium following IR. CDR1AS can increase the occurrence of autosis after IR. CDR1AS reduces the phosphorylation of ULK1, promoting the formation of autophagosomes. CDR1AS binds to LAMP2 and blocks the autophagosome clearance pathway. The specific mechanism of CDR1AS regulating IR is achieved by regulating autosis.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"219-237"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare variants in cardiomyopathy genes predispose to cardiac injury in severe COVID-19 patients of African or Hispanic ancestry.","authors":"Hui-Qi Qu, Matthew S Delfiner, Chethan Gangireddy, Anjali Vaidya, Kenny Nguyen, Isaac R Whitman, JuFang Wang, Jianliang Song, Michael R Bristow, Charles F McTiernan, Glenn S Gerhard, Hakon Hakonarson, Arthur M Feldman","doi":"10.1007/s00109-024-02510-z","DOIUrl":"10.1007/s00109-024-02510-z","url":null,"abstract":"<p><p>In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2. To test this hypothesis, we analyzed our WES data generated from a cohort of 325 patients sequentially admitted for COVID-19 infection. In this predominantly minority population (53.9% African ancestry and 37.9% Hispanic/Latin ancestry), our initial analysis screen identified 263 variants that were identified as highly deleterious (HD) from a total of 26,661 variants of interest that represented 215 genes. Of those, we identified 46 genes (in 58 patients) harboring rare HD coding variants that were previously implicated in dilated cardiomyopathy and were considered as disease initiators for the severe COVID-19 in this study. These findings offer valuable insights into the molecular mechanisms and genetic susceptibility to heart injury in severe COVID-19. KEY MESSAGES: COVID-19 may cause cardiac damage in some affected patients without a plausible biological explanation. Our study reveals an enrichment of highly deleterious variants linked to cardiomyopathy in severe COVID-19 patients. Genetic profiling unveils the molecular basis of severe COVID-19-related heart injury, potentially aiding in patient stratification.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"175-185"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering metabolic shifts in Gaucher disease type 1: a multi-omics study.","authors":"Franklin Ducatez, Marc G Berger, Carine Pilon, Thomas Plichet, Céline Lesueur, Juliette Berger, Nadia Belmatoug, Stéphane Marret, Soumeya Bekri, Abdellah Tebani","doi":"10.1007/s00109-024-02512-x","DOIUrl":"10.1007/s00109-024-02512-x","url":null,"abstract":"<p><p>Gaucher disease (GD), an autosomal recessive lysosomal disorder, primarily affects the lysosomal enzyme β-glucocerebrosidase (GCase), leading to glucosylceramide accumulation in lysosomes. GD presents a wide spectrum of clinical manifestations. This study deploys immune-based proteomics and mass spectrometry-based metabolomics technologies to comprehensively investigate the biochemical landscape in 43 deeply phenotyped type 1 GD patients compared to 59 controls. Conventional and systems biology approaches have been used to analyze the data. The results show promising biological imprints. Elevated phosphatidylcholines in GD patients suggest altered lipid metabolism, potentially due to their increased synthesis. This points to endoplasmic reticulum stress and impaired lipid trafficking, commonly seen in lysosomal diseases. GD patients exhibit an inflammatory profile with elevated cytokines and autoimmune-like inflammation, even in treated patients, highlighting the complexity of GD-related immune imbalances. Mitochondrial dysfunction clues are found through increased oxidative stress markers and altered acylcarnitine profiles in GD patients, suggesting mitochondrial membrane dysfunction affecting carnitine-carrying capacity. Furthermore, platelet count, splenectomy, treatment, and clinical traits were associated with specific omics features, providing insights into GD's clinical heterogeneity and potential diagnostic markers. Autophagy inhibition appears pivotal in GD, driving lipid synthesis, impaired mitochondrial function, and inflammation through chronic activation of mTORC1. Despite limitations like focusing on type 1 GD and using targeted omics approaches, this study provides valuable insights into GD metabolic and immune dysregulation. It lays the basis for future comprehensive investigations into GD manifestations with broader scope and molecular coverage. KEY MESSAGES: The study sheds light on metabolic and immune dysregulation in Gaucher disease. Gaucher disease patients showed elevated phosphatidylcholines, disrupted lipid metabolism, and inflammation profiles. Signs of mitochondrial dysfunction are evident in Gaucher disease patients, with autophagy inhibition significantly affecting lipid synthesis, mitochondrial function, and inflammation via chronic activation of mTORC1.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"187-203"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VSMC-specific TRPC1 deletion attenuates angiotensin II-induced hypertension and cardiovascular remodeling.","authors":"Xin Wen, Yuefeng Peng, Wenqing Yang, Yuzhong Zhu, Fan Yu, Li Geng, Xianfeng Wang, Xiaoyan Wang, Xiaodong Zhang, Yi Tang, Lei Feng, Tingting Zhou, Hongliang Jia, Liu Yang","doi":"10.1007/s00109-024-02509-6","DOIUrl":"10.1007/s00109-024-02509-6","url":null,"abstract":"<p><p>Transient receptor potential canonical 1 (TRPC1) channel, a Ca²⁺-permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. KEY MESSAGES: AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice. TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling. Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"205-218"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of lncRNA in the differentiation of adipose-derived stem cells: from functions to mechanism.","authors":"Yujing Wang, Yuxi Zhou, Kun Li","doi":"10.1007/s00109-024-02507-8","DOIUrl":"10.1007/s00109-024-02507-8","url":null,"abstract":"<p><p>Adipose-derived stem cells (ADSCs) have become one of the best seed cells widely studied and concerned in tissue engineering because of their rich sources and excellent multi-directional differentiation ability, which are expected to play a practical application role in tissue defect, osteoporosis, plastic surgery, and other fields. However, the differentiation direction of ADSCs is regulated by complex factors. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 500 nucleotides that do not encode proteins and can act as signaling RNAs in response to intracellular and extracellular stimuli. Recently, accumulating evidence has revealed that lncRNAs could regulate the cell cycle and differentiation direction of ADSCs through various mechanisms, including histone modification, binding to RNA-binding proteins, and regulating the expression of miRNAs. Therefore, enriching and elucidating its mechanism of action as well as targeting lncRNAs to regulate ADSCs differentiation have potential prospects in tissue regeneration applications such as bone, blood vessels, and adipose. In this review, we summarize the role and mechanism of lncRNAs and its complexes in the multi-directional differentiation of ADSCs and discuss some potential approaches that can exert therapeutic effects on tissue defects by modulating the expression level of lncRNAs in ADSCs. Our work might provide some new research directions for the clinical applications of tissue engineering.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"125-135"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}