Molecular Medicine最新文献

{"title":"Occurrence and role of Tph cells in various renal diseases.","authors":"Junyi Ren, Kuai Ma, Xiangheng Lu, Haoyu Peng, Jia Wang, Moussa Ide Nasser, Chi Liu","doi":"10.1186/s10020-024-00919-3","DOIUrl":"10.1186/s10020-024-00919-3","url":null,"abstract":"<p><p>A new population of peripheral helper T (Tph) cells has been identified and contributed to various autoimmune diseases. Tph cells can secrete interleukin-21 (IL-21), interferon (IFN) and C-X-C motif chemokine ligand 13 (CXCL13) to moderate renal disease. Moreover, Tph cells can congregate in huge numbers and immerse within inflamed tissue. Compared to Tfh cells, Tph cells express high programmed cell death protein 1 (PD-1), major histocompatibility complex II (MHC-II), C-C chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) but often lack expression of the chemokine receptor C-X-C chemokine receptor 5 (CXCR5). They display features distinct from other T cells, which are uniquely poised to promote responses and antibody production of B cells within pathologically inflamed non-lymphoid tissues and a key feature of Tph cells. In this review, we summarize recent findings on the role of Tph cells in chronic kidney disease, acute kidney injury, kidney transplantation and various renal diseases.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"174"},"PeriodicalIF":6.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drp1 acetylation mediated by CDK5-AMPK-GCN5L1 axis promotes cerebral ischemic injury via facilitating mitochondrial fission.","authors":"Jiejie Zhang, Shan Wang, Haitao Zhang, Xiaotong Yang, Xin Ren, Lei Wang, Yihan Yang, Yi Yang, Ya Wen","doi":"10.1186/s10020-024-00948-y","DOIUrl":"10.1186/s10020-024-00948-y","url":null,"abstract":"<p><p>The aberrant acetylation of mitochondrial proteins is involved in the pathogenesis of multiple diseases including neurodegenerative diseases and cerebral ischemic injury. Previous studies have shown that depletion of mitochondrial NAD+, which is necessary for mitochondrial deacetylase activity, leads to decreased activity of mitochondrial deacetylase and thus causes hyperacetylation of mitochondrial proteins in ischemic brain tissues, which results in altered mitochondrial dynamics. However, it remains largely unknown about how mitochondrial dynamics-related protein Drp1 is acetylated in ischemic neuronal cells and brain tissues. Here, we showed that Drp1 and GCN5L1 expression was up-regulated in OGD-treated neuronal cells and ischemic brain tissues induced by dMCAO, accompanied by the increased mitochondrial fission, mtROS accumulation, and cell apoptosis. Further, we confirmed that ischemia/hypoxia promoted Drp1 interaction with GCN5L1 in neuronal cells and brain tissues. GCN5L1 knockdown attenuated, while its overexpression enhanced Drp1 acetylation and mitochondrial fission, indicating that GCN5L1 plays a crucial role in ischemia/hypoxia-induced mitochondrial fission by acetylating Drp1. Mechanistically, ischemia/hypoxia induced Drp1 phosphorylation by CDK5 upregulation-mediated activation of AMPK in neuronal cells, which in turn facilitated the interaction of GCN5L1 with Drp1, thus enhancing Drp1 acetylation and mitochondrial fission. Accordingly, inhibition of AMPK alleviated ischemia/hypoxia- induced Drp1 acetylation and mitochondrial fission and protected brain tissues from ischemic damage. These findings provide a novel insight into the functional roles of GCN5L1 in regulating Drp1 acetylation and identify a previously unrecognized CDK5-AMPK-GCN5L1 pathway that mediates the acetylation of Drp1 in ischemic brain tissues.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"173"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylcholine receptor-β inhibition by interleukin-6 in skeletal muscles contributes to modulating neuromuscular junction during aging.","authors":"Yanling Zhao, Han Yan, Ke Liu, Jiangping Ma, Wenlan Sun, Hejin Lai, Hongli Li, Jianbang Gu, He Huang","doi":"10.1186/s10020-024-00943-3","DOIUrl":"10.1186/s10020-024-00943-3","url":null,"abstract":"<p><strong>Background: </strong>Aging-related strength decline contributes to physiological deterioration and is a good predictor of poor prognosis. However, the mechanisms underlying neuromuscular junction disorders affecting contraction in aging are not well described. We hypothesized that the autocrine effect of interleukin (IL)-6 secreted by skeletal muscle inhibits acetylcholine receptor (AChR) expression, potentially causing aging-related strength decline. Therefore, we investigated IL-6 and AChR β-subunit (AChR-β) expression in the muscles and sera of aging C57BL/6J mice and verified the effect of IL-6 on AChR-β expression.</p><p><strong>Methods: </strong>Animal experiments, in vitro studies, bioinformatics, gene manipulation, dual luciferase reporter gene assays, and chromatin immunoprecipitation experiments were used to explore the role of the transcription cofactor peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) and its interacting transcription factors in the IL-6-mediated regulation of AChR-β expression.</p><p><strong>Results: </strong>IL-6 expression gradually increased during aging, inhibiting AChR-β expression, which was reversed by tocilizumab. Both tocilizumab and the PGC1α agonist reversed the inhibiting effect of IL-6 expression on AChR-β. Compared to inhibition of signal transducer and activator of transcription 3, extracellular signal-regulated kinases 1/2 (ERK1/2) inhibition suppressed the effects of IL-6 on AChR-β and PGC1α. In aging mouse muscles and myotubes, myocyte enhancer factor 2 C (MEF2C) was recruited by PGC1α, which directly binds to the AChR-β promoter to regulate its expression.</p><p><strong>Conclusions: </strong>This study verifies AChR-β regulation by the IL-6/IL-6R-ERK1/2-PGC1α/MEF2C pathway. Hence, evaluating muscle secretion, myokines, and AChRs at an earlier stage to determine pathological progression is important. Moreover, developing intervention strategies for monitoring, maintaining, and improving muscle structure and function is necessary.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"171"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/β-catenin axis.","authors":"Yi Cui, Haojie Wen, Jinyong Tang, Jiawen Chen, Juan Zhou, Minghua Hou, Xiaohan Rong, Yuanzhao Lan, Qiong Wu","doi":"10.1186/s10020-024-00941-5","DOIUrl":"10.1186/s10020-024-00941-5","url":null,"abstract":"<p><strong>Background: </strong>The role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/β-catenin pathway.</p><p><strong>Methods: </strong>The expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect β-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR).</p><p><strong>Results: </strong>In both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced β-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with β-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression.</p><p><strong>Conclusions: </strong>ELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating β-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-β-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"172"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1/STAT3/HIF-1α signaling.","authors":"FengQi Zhang, YiYang Zhang, JiaWang Zhou, Ying Cai, ZhiYu Li, Jing Sun, ZhiJun Xie, GuiFeng Hao","doi":"10.1186/s10020-024-00929-1","DOIUrl":"10.1186/s10020-024-00929-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Object: &lt;/strong&gt;To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Quercetin's action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation e","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"170"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewriting cellular fate: epigenetic interventions in obesity and cellular programming.","authors":"Rui-Lin Li, Sheng Kang","doi":"10.1186/s10020-024-00944-2","DOIUrl":"10.1186/s10020-024-00944-2","url":null,"abstract":"<p><p>External constraints, such as development, disease, and environment, can induce changes in epigenomic patterns that may profoundly impact the health trajectory of fetuses and neonates into adulthood, influencing conditions like obesity. Epigenetic modifications encompass processes including DNA methylation, covalent histone modifications, and RNA-mediated regulation. Beyond forward cellular differentiation (cell programming), terminally differentiated cells are reverted to a pluripotent or even totipotent state, that is, cellular reprogramming. Epigenetic modulators facilitate or erase histone and DNA modifications both in vivo and in vitro during programming and reprogramming. Noticeably, obesity is a complex metabolic disorder driven by both genetic and environmental factors. Increasing evidence suggests that epigenetic modifications play a critical role in the regulation of gene expression involved in adipogenesis, energy homeostasis, and metabolic pathways. Hence, we discuss the mechanisms by which epigenetic interventions influence obesity, focusing on DNA methylation, histone modifications, and non-coding RNAs. We also analyze the methodologies that have been pivotal in uncovering these epigenetic regulations, i.e., Large-scale screening has been instrumental in identifying genes and pathways susceptible to epigenetic control, particularly in the context of adipogenesis and metabolic homeostasis; Single-cell RNA sequencing (scRNA-seq) provides a high-resolution view of gene expression patterns at the individual cell level, revealing the heterogeneity and dynamics of epigenetic regulation during cellular differentiation and reprogramming; Chromatin immunoprecipitation (ChIP) assays, focused on candidate genes, have been crucial for characterizing histone modifications and transcription factor binding at specific genomic loci, thereby elucidating the epigenetic mechanisms that govern cellular programming; Somatic cell nuclear transfer (SCNT) and cell fusion techniques have been employed to study the epigenetic reprogramming accompanying cloning and the generation of hybrid cells with pluripotent characteristics, etc. These approaches have been instrumental in identifying specific epigenetic marks and pathways implicated in obesity, providing a foundation for developing targeted therapeutic interventions. Understanding the dynamic interplay between epigenetic regulation and cellular programming is crucial for advancing mechanism and clinical management of obesity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"169"},"PeriodicalIF":6.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA.","authors":"Azar Abbas, Xiaosheng Huang, Aftab Ullah, Lishi Luo, Wenqun Xi, Yuanjiao Qiao, Kun Zeng","doi":"10.1186/s10020-024-00940-6","DOIUrl":"10.1186/s10020-024-00940-6","url":null,"abstract":"<p><strong>Background: </strong>A spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.</p><p><strong>Objective: </strong>This study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).</p><p><strong>Methods: </strong>iPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.</p><p><strong>Results: </strong>The results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.</p><p><strong>Conclusion: </strong>These results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"168"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology, molecular docking and experimental verification to explore the therapeutic effect and potential mechanism of nomilin against triple-negative breast cancer.","authors":"Zhixuan Wu, Haoyi Xiang, Xiaowu Wang, Rongrong Zhang, Yangyang Guo, Liangchen Qu, Jingyao Zhou, Yanyi Xiao","doi":"10.1186/s10020-024-00928-2","DOIUrl":"https://doi.org/10.1186/s10020-024-00928-2","url":null,"abstract":"<p><strong>Background: </strong>Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action.</p><p><strong>Methods: </strong>We employed weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the GeneCards database to identify potential targets for TNBC. Simultaneously, we utilized the Swiss Target Prediction, ChEMBL, and STITCH databases to identify potential targets of nomilin. The core targets and mechanisms of nomilin against TNBC were predicted through protein-protein interaction (PPI) network analysis, molecular docking, and enrichment analysis. The results of the network pharmacology were corroborated by conducting experiments.</p><p><strong>Results: </strong>A total of 17,204 TNBC targets were screened, and 301 potential targets of nomilin were identified. Through the PPI network, eight core targets of nomilin against TNBC were pinpointed, namely BCL2, Caspase3, CyclinD1, EGFR, HSP90AA1, KRAS, PARP1, and TNF. Molecular docking, molecular dynamics simulation and proteome microarray revealed that nomilin exhibits strong binding activity to these core proteins. Enrichment analysis results indicated that the anti-TNBC effect of nomilin is associated with PI3K/Akt pathway. In vitro and in vivo experiments have demonstrated that nomilin inhibits TNBC cell proliferation and migration while promoting cell apoptosis through the PI3K/Akt pathway.</p><p><strong>Conclusion: </strong>For the first time, the research effectively discovered the objectives and mechanisms of nomilin in combating TNBC using network pharmacology, molecular docking, molecular dynamics simulation, proteome microarray and experimental confirmation, presenting a hopeful approach for treating TNBC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"166"},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in hematological diseases.","authors":"Shuangping Ma, Yiran Qin, Wenjie Ren","doi":"10.1186/s10020-024-00936-2","DOIUrl":"https://doi.org/10.1186/s10020-024-00936-2","url":null,"abstract":"<p><p>The oncofetal mRNA-binding protein IGF2BP1 belongs to a conserved family of RNA-binding proteins. It primarily promotes RNA stability, regulates translation and RNA localization, and mediates gene expression through its downstream effectors. Numerous studies have demonstrated that IGF2BP1 plays crucial roles in embryogenesis and carcinogenesis. IGF2BP1-modulated cell proliferation, invasion, and chemo-resistance in solid tumors have attracted researchers' attention. Additionally, several studies have highlighted the importance of IGF2BP1 in hematologic malignancies and hematological genetic diseases, positioning it as a promising therapeutic target for hematological disorders. However, there is a lack of systematic summaries regarding the IGF2BP1 gene within the hematological field. In this review, we provide a comprehensive overview of the discovery and molecular structure of IGF2BP1, along with recent studies on its role in regulating embryogenesis. We also focus on the mechanisms by which IGF2BP1 regulates hematological malignancies through its interactions with its targeted mRNAs. Furthermore, we systematically elucidate the function and mechanism of IGF2BP1 in promoting fetal hemoglobin expression in adult hematopoietic stem/progenitor cells. Finally, we discuss the limitations and challenges of IGF2BP1 as a therapeutic target, offering insights into its prospects.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"165"},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.","authors":"Junming Huang, Tianle Ma, Chenzhong Wang, Zhe Wang, Xinyuan Wang, Bingxuan Hua, Chang Jiang, Zuoqin Yan","doi":"10.1186/s10020-024-00933-5","DOIUrl":"10.1186/s10020-024-00933-5","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.</p><p><strong>Methods: </strong>Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.</p><p><strong>Results: </strong>Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.</p><p><strong>Conclusion: </strong>Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"30 1","pages":"167"},"PeriodicalIF":6.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}