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ANXA1 and ARG2 drive T cell proliferation in ischemia-reperfusion injury: integrated bulk and single-cell transcriptomic analysis. 缺血再灌注损伤中ANXA1和ARG2驱动T细胞增殖:整体和单细胞转录组学分析
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-04 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1673163
Haofeng Zheng, Kaiming He, Jianchao Wei, Wangtianxu Zhou, Zhiyi Kong, Qingfu Dai, Jieyi Dong, Zihuan Luo, Qiquan Sun
{"title":"<i>ANXA1</i> and <i>ARG2</i> drive T cell proliferation in ischemia-reperfusion injury: integrated bulk and single-cell transcriptomic analysis.","authors":"Haofeng Zheng, Kaiming He, Jianchao Wei, Wangtianxu Zhou, Zhiyi Kong, Qingfu Dai, Jieyi Dong, Zihuan Luo, Qiquan Sun","doi":"10.3389/fcell.2025.1673163","DOIUrl":"10.3389/fcell.2025.1673163","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) represents a common pathophysiological condition and serves as a shared mechanism underlying diverse critical diseases, including acute kidney injury, myocardial infarction, and stroke. T cells are increasingly recognized as central mediators of immune responses during IRI; however, the mechanisms governing their proliferation remain poorly characterized. Herein, an integrative analysis of bulk and single-cell transcriptomic datasets across multiple organ models was performed to investigate the role of T cell proliferation-related genes in IRI. We identified <i>ANXA1</i> and <i>ARG2</i> as key IRI-associated genes, both of which exhibited consistent upregulation during the early stages of injury. Immune infiltration analysis demonstrated that <i>ANXA1</i> expression correlated most strongly with central memory CD4<sup>+</sup> T cell infiltration, whereas <i>ARG2</i> was linked to T helper 17 cell infiltration. Drug prediction and molecular dynamics simulation further identified Hydrocortamate and NS6180 as potential therapeutic agents targeting T cell proliferation. Single-cell RNA sequencing not only confirmed the active involvement of T cells in IRI progression but also highlighted <i>ANXA1</i> as a particularly prominent regulator. A renal IRI model was also used to further confirm altered T cell activity and differential expression of these key genes <i>in vivo</i>. Collectively, these findings elucidate the molecular mechanisms driving T cell proliferation in IRI, positioning <i>ANXA1</i> and <i>ARG2</i> as promising pan-organ IRI biomarkers and therapeutic targets for mitigating tissue damage and promoting repair.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1673163"},"PeriodicalIF":4.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unlocking hematopoietic stem cell potential: integrative computational approaches for genomic and transcriptomic analysis. 解锁造血干细胞潜能:基因组和转录组学分析的综合计算方法。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1589823
Pawan Kumar Raghav, Basudha Banerjee, Rajni Chadha
{"title":"Unlocking hematopoietic stem cell potential: integrative computational approaches for genomic and transcriptomic analysis.","authors":"Pawan Kumar Raghav, Basudha Banerjee, Rajni Chadha","doi":"10.3389/fcell.2025.1589823","DOIUrl":"10.3389/fcell.2025.1589823","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) sustain lifelong hematopoiesis through their capacity for self-renewal and multilineage differentiation. However, the isolation and functional characterization of HSCs remain challenging due to their cellular heterogeneity and dynamically regulated transcriptional and epigenetic landscapes. Advances in experimental and computational biology, including single-cell RNA sequencing (scRNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), network inference algorithms, and machine learning, have improved our ability to resolve transcriptional states, trace lineage trajectories, and reconstruct gene regulatory networks (GRN) at single-cell resolution. These approaches enable the discovery of novel HSC subtypes and regulatory factors, and facilitate the integration of multi-omics data to uncover epigenetic and transcriptional mechanisms that drive stem cell fate decisions. Additionally, machine learning models trained on high-throughput datasets provide predictive power for identifying novel enhancers, transcription factors, and therapeutic targets. This review underscores the synergistic role of computational tools in deciphering HSC biology and highlights their potential to improve stem cell therapies and precision treatments for hematologic disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1589823"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanism of Huaiqihuang (HQH) against cyclophosphamide (CYP)-induced hippocampal neurotoxicity based on network pharmacology, molecular docking and experimental verification. 基于网络药理学、分子对接和实验验证的槐七黄抗环磷酰胺(CYP)诱导海马神经毒性机制
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1629110
Yueming Zhang, Fengwei Huang, Jinghui Zhai, Jingmeng Sun, Boyu Li, Sixi Zhang
{"title":"Mechanism of Huaiqihuang (HQH) against cyclophosphamide (CYP)-induced hippocampal neurotoxicity based on network pharmacology, molecular docking and experimental verification.","authors":"Yueming Zhang, Fengwei Huang, Jinghui Zhai, Jingmeng Sun, Boyu Li, Sixi Zhang","doi":"10.3389/fcell.2025.1629110","DOIUrl":"10.3389/fcell.2025.1629110","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CYP) is widely used for the treatment of cancer and autoimmune diseases. However, neurotoxicity accompanied with application of CYP seriously affects the final clinical outcome. Huaiqihuang (HQH) is a Chinese herbal complex with immunomodulatory effect and widely used for treating various diseases. The present research was conducted to evaluate the protective effect of HQH against CYP-induced neurotoxicity and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Sprague-Dawley rats were randomly divided into four groups (10 per group): the CYP-only group (single dose of 200 mg/kg), low- and high-dose HQH + CYP groups (pretreatment with 3 or 6 g/kg HQH for 5 days), and control (saline) group. Histopathological analysis and behavioral tests was used to evaluate the therapeutic effects of HQH on CYP-induced neurotoxicity. Network pharmacology, molecular docking, and Western blot were employed to assess the anti-neurotoxicity mechanisms.</p><p><strong>Results: </strong>Both doses of HQH restored histopathological aberrations, oxidative stress and inflammation caused by CYP in rats. Behavioral tests showed that HQH pretreatment improved motor coordination and balance in CYP-treated rats. Network pharmacology identified core targets including HSP90AA1, TP53, MAPK1, AKT1, RELA, TNF. Molecular docking revealed that TNF, HSP90AA1, TP53, and MAPK1 had strong binding affinities with CYP. Experimental validation using Western blot confirmed that HQH significantly decreased the protein expression of TNF, HSP90AA1, TP53, and MAPK1 in hippocampal tissues.</p><p><strong>Conclusion: </strong>HQH mitigates CYP-induced hippocampal neurotoxicity by decreasing oxidative stress, and inflammation, with HSP90AA1 being a key target, providing a novel therapeutic strategy for chemotherapy-associated cognitive impairment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1629110"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Testicular immunosenescence: a key player in age-related spermatogenic decline. 更正:睾丸免疫衰老:与年龄相关的生精能力下降的关键因素。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1687852
Ming-Wei Zhan, Mu-Hua Zhou, Bin-Bin Zhao, Xiao-Jie Bao, Yibo Chen, Jingyu Zhu
{"title":"Correction: Testicular immunosenescence: a key player in age-related spermatogenic decline.","authors":"Ming-Wei Zhan, Mu-Hua Zhou, Bin-Bin Zhao, Xiao-Jie Bao, Yibo Chen, Jingyu Zhu","doi":"10.3389/fcell.2025.1687852","DOIUrl":"10.3389/fcell.2025.1687852","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcell.2025.1669826.].</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1687852"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SPARC aberrant methylation in idiopathic pulmonary fibrosis: an explorative study. 特发性肺纤维化中SPARC异常甲基化:一项探索性研究。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1639844
Federico Pio Fabrizio, Angelo Sparaneo, Flavia Centra, Francesco Delli Muti, Paola Parente, Massimiliano Copetti, Marco Donatello Delcuratolo, Antonio Rossi, Elisa Gili, Giulio Rossi, Paolo Graziano, Lucia Anna Muscarella
{"title":"<i>SPARC</i> aberrant methylation in idiopathic pulmonary fibrosis: an explorative study.","authors":"Federico Pio Fabrizio, Angelo Sparaneo, Flavia Centra, Francesco Delli Muti, Paola Parente, Massimiliano Copetti, Marco Donatello Delcuratolo, Antonio Rossi, Elisa Gili, Giulio Rossi, Paolo Graziano, Lucia Anna Muscarella","doi":"10.3389/fcell.2025.1639844","DOIUrl":"10.3389/fcell.2025.1639844","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease (ILD) characterized by progressive accumulation of extracellular matrix in the lung and dysregulated activation of specific signaling pathways. Recent advances in the understanding of the biological bases of IPF identified the silencing of secreted protein acidic and rich in cysteine (SPARC) as a key modulator in the pathogenesis of IPF, although the mechanisms underlying the SPARC aberrant modulation remain to be fully elucidated.</p><p><strong>Methods: </strong>Here we investigated the aberrant methylation at the promoter gene region as a possible mechanism of SPARC deregulation in IPF. Formalin-fixed paraffin-embedded (FFPE) tissues from a cohort of 44 patients with IPF and from a control-group of 23 non-idiopathic pulmonary fibrosis (NIPF) were analyzed. DNA methylation analysis at the <i>SPARC</i> promoter region was assessed by quantitative methylation-specific PCR analysis (QMSP) and a total of 11 CpGs located in the gene promoter island were evaluated.</p><p><strong>Results: </strong>Methylation levels were found to be significantly higher (p < 0.004, Mann-Whitney test) in 44 IPF samples (methylated using the optimal cut-off 20/44, 45%) compared to NIPF surgical biopsies (methylated using the optimal cut-off 3/23, 13%). At the <i>in vitro</i> level, we observed an inverse correlation between SPARC mRNA levels and hypermethylation under 5-Aza-2'-deoxycytidine (5-Aza-CdR) treatment when a primary fibrotic cell line was treated, whereas any variations were observed treating non-fibrotic cells.</p><p><strong>Discussion: </strong>Our explorative study suggests that promoter methylation of the <i>SPARC</i> gene is linked to IPF but not to NIPF, and could represent a potential molecular marker of disease, thus warranting further investigations on larger cohorts.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1639844"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR/Cas-edited iPSCs and mesenchymal stem cells: a concise review of their potential in thalassemia therapy. CRISPR/ cas编辑的iPSCs和间充质干细胞:对其在地中海贫血治疗中的潜力的简要回顾
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1595897
Jiaojiao Shu, Xin Xie, Sixi Wang, Zuochen Du, Pei Huang, Yan Chen, Zhixu He
{"title":"CRISPR/Cas-edited iPSCs and mesenchymal stem cells: a concise review of their potential in thalassemia therapy.","authors":"Jiaojiao Shu, Xin Xie, Sixi Wang, Zuochen Du, Pei Huang, Yan Chen, Zhixu He","doi":"10.3389/fcell.2025.1595897","DOIUrl":"10.3389/fcell.2025.1595897","url":null,"abstract":"<p><p>Thalassemia, a prevalent single-gene inherited disorder, relies on hematopoietic stem cell or bone marrow transplantation as its definitive treatment. However, the scarcity of suitable donors and the severe complications from anemia and iron overload pose significant challenges. An immediate need exists for a therapeutic method that addresses both the illness and its associated complications. Advancements in stem cell technology and gene-editing methods, such as clustered regularly interspaced short palindromic repeats along with its associated protein (CRISPR/Cas), offer encouraging prospects for a therapy that could liberate patients from the need for ongoing blood transfusions and iron chelation treatments. The potential of genetic reprogramming using induced pluripotent stem cells (iPSCs) to address thalassemia is highly promising. Furthermore, mesenchymal stem cells (MSCs), recognized for their capacity to self-renew and differentiate into multiple lineages that include bone, cartilage, adipose tissue, and liver, demonstrate potential in alleviating several complications faced by thalassemia patients, including osteoporosis, cirrhosis, heart conditions, respiratory issues, and immune-related disorders. In this review, we synthesize and summarize relevant studies to assess the therapeutic potential and predict the curative effects of these cellular approaches.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1595897"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem/progenitor cell-based therapy for Duchenne muscular dystrophy. 基于干细胞/祖细胞的治疗杜氏肌营养不良症。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1640275
Tsukasa Tominari, Chaitra Sathyaprakash, Yoshitsugu Aoki
{"title":"Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.","authors":"Tsukasa Tominari, Chaitra Sathyaprakash, Yoshitsugu Aoki","doi":"10.3389/fcell.2025.1640275","DOIUrl":"10.3389/fcell.2025.1640275","url":null,"abstract":"<p><p>Duchenne muscular dystrophy is a genetic disease where loss of sarcolemma-associated protein, dystrophin, leads to progressive muscle wasting, and eventual loss of life from complications linked to cardiac deficits. Currently, numerous molecular therapies to restore dystrophin have entered clinical trials. However, the therapeutic benefits of these strategies in promoting tissue regeneration and reducing fibrosis remain limited. Stem/progenitor cell-based therapy in DMD patients is a promising strategy to promote muscle regeneration, though the conditions of transplantation and pre-treatments of numerous cell types are still being optimized. Several cell types with different properties and origins, such as myogenic stem/progenitor cells, mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs), have been studied for treating DMD. Myogenic stem/progenitor cells derived from healthy donors are expected to restore the number of myofibers as well as dystrophin expression in DMD muscles. MSCs derived from various tissues, including umbilical cord, have immunosuppressive properties and are expected to ameliorate DMD phenotypes in combination with other gene therapies. In this review, we will summarize the challenges that must be overcome to allow for successful DMD muscle tissue regeneration and review the latest findings in stem/progenitor cell-based DMD therapy. We will focus on the pre-conditioning of cells for replacement therapies and treatment of the disease niche to improve muscle fiber integration.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1640275"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Specific inhibition of glutamine synthase involved in the metabolic pathway of amino acids is associated with anti-arthritic effects of sinomenine hydrochloride. 参与氨基酸代谢途径的谷氨酰胺合成酶的特异性抑制与盐酸青藤碱的抗关节炎作用有关。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1658089
Gejing Li, Zhaoli Su, Yuanyuan Tang, Hong Huang, Junlan Zhang, Ye Lin, Qin Zhang, Xiong Cai
{"title":"Specific inhibition of glutamine synthase involved in the metabolic pathway of amino acids is associated with anti-arthritic effects of sinomenine hydrochloride.","authors":"Gejing Li, Zhaoli Su, Yuanyuan Tang, Hong Huang, Junlan Zhang, Ye Lin, Qin Zhang, Xiong Cai","doi":"10.3389/fcell.2025.1658089","DOIUrl":"10.3389/fcell.2025.1658089","url":null,"abstract":"<p><p>Sinomenine (SIN) is the key bioactive alkaloid isolated from Sinomenium acutum which has been prescribed commonly in Chinese medicine for managing rheumatic disorders. Despite its clinical relevance, the metabolic mechanisms underlying its therapeutic effects remain insufficiently explored, particularly in relation to amino acid dysregulation in rheumatoid arthritis (RA). The anti-arthritic efficacy of sinomenine hydrochloride (SH) was tested in adjuvant-induced arthritis in rats utilizing clinical scoring and histological analysis. Plasma metabolomics was employed to identify SH-mediated changes in amino acid-related metabolic profiles. Key metabolic pathways and targets were examined using computational docking and surface plasmon resonance (SPR) assay. The interaction of SH and molecular targets was further validated in RA fibroblast-like synoviocytes (RA-FLS). SH at dose of 100 mg/kg significantly alleviated disease progression of AIA, as evidenced by reduced paw edema and inhibited histopathological changes. Metabolomic analyses identified 94 potential plasma biomarkers linked to pathways of valine/leucine/isoleucine biosynthesis, glycine/serine/threonine metabolism, phenylalanine metabolism, and alanine/aspartate/glutamate metabolism. Molecular docking and SPR identified that SH specifically targeted the glutamine synthase (GS/GLUL) (KD = 7.12 μM). Experimental validation confirmed that SH (50-200 μM) significantly inhibited GS activity and GLUL expression and consequently decreased glutamine levels in RA-FLS. In conjunction SH exerts significant anti-arthritic effects, partly by modulating the metabolic profiles of related amino acids via selective inhibition of GS-mediated <i>de novo</i> Gln synthesis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1658089"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Specialised features of melanosomes in health and disease in the retinal pigment epithelium. 视网膜色素上皮健康和疾病中黑素体的特化特征。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1593840
Dilyana Doncheva, Emily R Eden, Clare E Futter
{"title":"Specialised features of melanosomes in health and disease in the retinal pigment epithelium.","authors":"Dilyana Doncheva, Emily R Eden, Clare E Futter","doi":"10.3389/fcell.2025.1593840","DOIUrl":"10.3389/fcell.2025.1593840","url":null,"abstract":"<p><p>This mini-review focuses on melanosome biogenesis, positioning and function in the retinal pigment epithelium (RPE) where melanosomes absorb light scatter and protect against the harmful effects of photo-oxidation. RPE melanosomes share a common biogenesis pathway with those of skin melanocytes but are made primarily embryonically and are retained by the RPE throughout life. They do however move from the cell body into the apical processes which, in mammalian RPE, is regulated by a machinery related to that regulating melanosome distribution in skin melanocytes. Melanosomes in the RPE make extensive membrane contacts with the ER and mitochondria although their role in adult RPE remains to be fully established. Albinism is associated with multiple visual defects and reduced or absent pigmentation in melanosomes has implications for long term visual health. Age-related changes in melanosomes have been implicated in retinal degenerative disease, including age-related macular disease (AMD). The lysosomes of the RPE have an unparalleled degradative burden arising from the daily phagocytosis of the distal tips of photoreceptor outer segments, which is part of a daily process of outer segment renewal. A failure to fully process the phagocytosed outer segments leads to a build-up of the toxic ageing pigment, lipofuscin, which accumulates in all ageing RPE. Melanolipofuscin also accumulates in the RPE with age and may result from melanin-mediated degradation of lipofuscin through melanin chemiexcitation. Age-related loss of melanosome-mediated protection could be an important component of age-related visual decline.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1593840"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The m6A demethylase FTO suppresses glioma proliferation by regulating the EREG/PI3K/Akt signaling pathway. m6A去甲基化酶FTO通过调控EREG/PI3K/Akt信号通路抑制胶质瘤增殖。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1667990
Yong Zhai, Caili Li, Lihui Cao, Shen Zhang, Xiao Liu, Junwei Ren, Yue Liu
{"title":"The m6A demethylase FTO suppresses glioma proliferation by regulating the EREG/PI3K/Akt signaling pathway.","authors":"Yong Zhai, Caili Li, Lihui Cao, Shen Zhang, Xiao Liu, Junwei Ren, Yue Liu","doi":"10.3389/fcell.2025.1667990","DOIUrl":"10.3389/fcell.2025.1667990","url":null,"abstract":"<p><strong>Background: </strong>Glioma, the most prevalent primary intracranial tumor, is characterized by aggressive proliferation and formidable treatment challenges. The N6-methyladenosine (m6A) demethylase, Fat mass and obesity-associated protein (FTO), is a critical regulator of gene expression, but its precise role in glioma remains controversial. This study aimed to elucidate the function and underlying molecular mechanisms of FTO in glioma progression.</p><p><strong>Methods: </strong>We integrated bioinformatic analysis of 1,027 glioma patients from public cohorts (TCGA and CGGA) with a comprehensive experimental approach. <i>In vitro</i> studies in U251 and U87MG glioma cells involved gain- and loss-of-function assays to assess proliferation, colony formation, and cell cycle progression. Mechanistic investigations included Western blotting, qRT-PCR, and mRNA stability assays. An <i>in vivo</i> subcutaneous xenograft model was used to validate the tumor-suppressive role of FTO.</p><p><strong>Results: </strong>Our analysis revealed that lower FTO expression is significantly associated with higher tumor grade and poorer overall survival in glioma patients. Functionally, FTO overexpression inhibited proliferation and induced G1 phase cell cycle arrest, whereas FTO knockdown enhanced these malignant phenotypes. Mechanistically, we identified Epiregulin (EREG) as a key downstream target of FTO. Loss of FTO increased global m6A levels and enhanced EREG mRNA stability, leading to its upregulation. This, in turn, activated the PI3K/Akt signaling pathway, evidenced by increased phosphorylation of PI3K and Akt and subsequent downregulation of p53 and p21. The <i>in vivo</i> model confirmed that FTO overexpression suppressed tumor growth, while its knockdown accelerated it.</p><p><strong>Conclusion: </strong>Our findings establish FTO as a tumor suppressor in glioma. It inhibits proliferation by destabilizing EREG mRNA in an m6A-dependent manner, thereby inactivating the PI3K/Akt signaling cascade. These results highlight FTO as a potential prognostic biomarker and a promising therapeutic target for glioma.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1667990"},"PeriodicalIF":4.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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