Cells最新文献

{"title":"Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific <i>Adar1</i> Knockout Mice.","authors":"Lisa Zerad, Nadjet Gacem, Fanny Gayda, Lucie Day, Ketty Sinigaglia, Laurence Richard, Melanie Parisot, Nicolas Cagnard, Stephane Mathis, Christine Bole-Feysot, Mary A O'Connell, Veronique Pingault, Emilie Dambroise, Liam P Keegan, Jean Michel Vallat, Nadege Bondurand","doi":"10.3390/cells13231952","DOIUrl":"https://doi.org/10.3390/cells13231952","url":null,"abstract":"<p><p>Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of <i>Adar1</i> reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of <i>Adar1</i> mutant phenotypes. By analyzing RNA-Seq data from the sciatic nerves of mouse pups after conditional neural crest deletion of <i>Adar1</i> (<i>Adar1</i>cKO), we here identified the transcription factors deregulated in <i>Adar1</i>cKO mutants compared to the controls. Through <i>Adar1</i>;<i>Mavs</i> and <i>Adar1</i>cKO;<i>Egr1</i> double-mutant mouse rescue analyses, we then highlighted that the aberrant activation of the Mavs adapter protein and overexpression of the early growth response 1 (EGR1) transcription factor contribute to the <i>Adar1</i> deletion associated defects in Schwann cell development in vivo. In silico and in vitro gene regulation studies additionally suggested that EGR1 might mediate this inhibitory effect through the aberrant regulation of EGR2-regulated myelin genes. We thus demonstrate the role of the Mda5/Mavs pathway, but also that of the Schwann cell transcription factors in <i>Adar1-</i>associated peripheral myelination defects.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Class of FKBP12 Ligands Rescues Premature Aging Phenotypes Associated with Myotonic Dystrophy Type 1.","authors":"Mikel García-Puga, Gorka Gerenu, Ariadna Bargiela, Jorge Espinosa-Espinosa, Laura Mosqueira-Martín, Maialen Sagartzazu-Aizpurua, Jesús M Aizpurua, Ainara Vallejo-Illarramendi, Rubén Artero, Adolfo López de Munain, Ander Matheu","doi":"10.3390/cells13231939","DOIUrl":"https://doi.org/10.3390/cells13231939","url":null,"abstract":"<p><p><b>Background:</b> Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder clinically characterized by progressive muscular weakness and multisystem degeneration, which correlates with the size of CTG expansion and MBLN decrease. These changes induce a calcium and redox homeostasis imbalance in several models that recapitulate the features of premature tissue aging. In this study, we characterized the impact of a new family of FKBP12 ligands (generically named MPs or MP compounds) designed to stabilize FKBP12 binding to the ryanodine receptors and normalize calcium dysregulation under oxidative stress. <b>Methods:</b> Human primary fibroblasts from DM1 patients and control donors, treated with MP compounds or not, were used for functional studies of cell viability, proliferation, and metabolism. The gene expression profile in treated cells was determined using RNA sequencing. The impact of MP compounds in vivo was evaluated in a <i>Drosophila</i> model of the disease using locomotor activity and longevity studies. <b>Results:</b> The treatment with different MP compounds reversed oxidative stress and impaired cell viability and proliferation, mitochondrial activity, and metabolic defects in DM1-derived primary fibroblasts. RNA sequencing analysis confirmed the restoration of molecular pathways related to calcium and redox homeostasis and additional pathways, including the cell cycle and metabolism. This analysis also revealed the rescue of alternative splicing events in DM1 fibroblasts treated with MP compounds. Importantly, treatment with MP compounds significantly extended the lifespan and improved the locomotor activity of a <i>Drosophila</i> model of the DM1 disease, and restored molecular defects characteristic of the disease in vivo. <b>Conclusions:</b> Our results revealed that MP compounds rescue multiple premature aging phenotypes described in DM1 models and decipher the benefits of this new family of compounds in the pre-clinical setting of DM1.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p.","authors":"Cheng-Yen Chuang, Bao-Wei Wang, Ying-Ju Yu, Wei-Jen Fang, Chiu-Mei Lin, Kou-Gi Shyu, Su-Kiat Chua","doi":"10.3390/cells13231942","DOIUrl":"https://doi.org/10.3390/cells13231942","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Rapid electrical stimulation (RES) of atrial fibroblasts plays a crucial role in AF pathogenesis, but the underlying molecular mechanisms remain unclear. This study investigates the regulatory axis involving MALAT1, miR-499a-5p, and SOX6 in human cardiac fibroblasts from adult atria (HCF-aa) under RES conditions.</p><p><strong>Methods: </strong>HCF-aa were subjected to RES at 0.5 V/cm and 10 Hz. The expression levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-499a-5p, and SRY-Box Transcription Factor 6 (SOX6) were measured using qPCR and Western blot analyses. Luciferase reporter assays were performed to confirm target relationships. The effects of MALAT1 siRNA, miR-499a-5p mimics/inhibitors, and SOX6 overexpression on gene expression and apoptosis were assessed.</p><p><strong>Results: </strong>RES increased exosomal MALAT1 expression, peaking at 2 h. MiR-499a-5p levels initially increased, then decreased at 2 h, coinciding with peak MALAT1 expression. SOX6 mRNA and protein levels increased, peaking at 4 and 6 h, respectively. Luciferase assays confirmed MALAT1 and SOX6 as miR-499a-5p targets. MALAT1 knockdown increased miR-499a-5p levels and reduced SOX6 expression. MiR-499a-5p overexpression decreased SOX6 levels and inhibited RES-induced apoptosis.</p><p><strong>Conclusion: </strong>In HCF-aa under RES, increased exosomal MALAT1 expression counteracts miR-499-5p's suppression of SOX6, suggesting that MALAT1-containing exsosomes derived from HCF-aa may offer a novel cell-free therapeutic approach for AF.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Treatment with Cannabinoid 2 Receptor Agonist HU-308 Ameliorates Cold Sensitivity in Mice with Traumatic Trigeminal Neuropathic Pain.","authors":"Simeng Ma, Yoki Nakamura, Suzuna Uemoto, Kenta Yamamoto, Kazue Hisaoka-Nakashima, Norimitsu Morioka","doi":"10.3390/cells13231943","DOIUrl":"https://doi.org/10.3390/cells13231943","url":null,"abstract":"<p><p>Post-traumatic trigeminal neuropathy (PTTN) is a sensory abnormality caused by injury to the trigeminal nerve during orofacial surgery. However, existing analgesics are ineffective against PTTN. Abnormal microglial activation in the caudal part of the spinal trigeminal nucleus caudal part (Sp5C), where the central trigeminal nerve terminals reside, plays an important role in PTTN pathogenesis. Therefore, regulating microglial activity in Sp5C appears to be an important approach to controlling pain in PTTN. Cannabinoid receptor 2 (CB₂) is expressed in immune cells including microglia, and its activation has anti-inflammatory effects. The current study demonstrates that the repeated intranasal administration of CB₂ agonist HU-308 ameliorates the infraorbital nerve cut (IONC)-induced hyperresponsiveness to acetone (cutaneous cooling). The therapeutic efficacy of oral HU-308 was found to be less pronounced in alleviating cold hypersensitivity in IONC mice compared to intranasal administration, indicating the potential advantages of the intranasal route. Furthermore, repeated intranasal administration of HU-308 suppressed the activation of Sp5C microglia in IONC mice. Additionally, pretreatment with the CB₂ antagonist, SR 144528, significantly blocked the anti-nociceptive effect of repeated intranasal administration of HU-308 on cold hypersensitization in IONC mice. These data suggest that the continuous stimulation of CB₂ ameliorates PTTN-induced pain via the inhibition of microglial activation. Thus, CB₂ agonists are potential candidates for novel therapeutic agents against PTTN.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Blood Leukocyte Subpopulation Changes in Reaction to an Acute Psychosocial Stressor as Compared to an Active Placebo-Stressor in Healthy Young Males: Mediating Effects of Major Stress-Reactive Endocrine Parameters.","authors":"Lisa-Marie Walther, Angelina Gideon, Christine Sauter, Marcel Leist, Petra H Wirtz","doi":"10.3390/cells13231941","DOIUrl":"https://doi.org/10.3390/cells13231941","url":null,"abstract":"<p><p>Psychosocial stress has been proposed to induce a redistribution of immune cells, but a comparison with an active placebo-psychosocial stress control condition is lacking so far. We investigated immune cell redistribution due to psychosocial stress compared to that resulting from an active placebo-psychosocial stress but otherwise identical control condition. Moreover, we tested for mediating effects of endocrine parameters and blood volume changes. The final study sample comprised 64 healthy young men who underwent either a psychosocial stress condition (Trier Social Stress Test; TSST; <i>n</i> = 38) or an active placebo-psychosocial stress control condition (PlacTSST; <i>n</i> = 26). Immune cell counts and hemoglobin, epinephrine, norepinephrine, ACTH, renin, and aldosterone levels, as well as those of saliva cortisol, were determined before and up to 30 min after the TSST/PlacTSST. The TSST induced greater increases in total leukocyte, monocyte, and lymphocyte levels as compared to the PlacTSST (<i>p</i>'s ≤ 0.001), but in not granulocyte counts. Neutrophil granulocyte counts increased in reaction to both the TSST and PlacTSST (<i>p</i>'s ≤ 0.001), while eosinophil and basophil granulocyte counts did not. The psychosocial stress-induced increases in immune cell counts from baseline to peak (i.e., +1 min after TSST cessation) were independently mediated by parallel increases in epinephrine (ab's ≤ -0.43; 95% CIs [LLs ≤ -0.66; ULs ≤ -0.09]). Subsequent decreases in immune cell counts from +1 min to +10 min after psychosocial stress cessation were mediated by parallel epinephrine, renin, and blood volume decreases (ab's ≥ 0.17; 95% CIs [LLs ≥ 0.02; ULs ≥ 0.35]). Our findings indicate that psychosocial stress specifically induces immune cell count increases in most leukocyte subpopulations that are not secondary to the physical or cognitive demands of the stress task. Increases in the number of circulating neutrophil granulocytes, however, are not psychosocial stress-specific and even occur in situations with a low probability of threat or harm. Our findings point to a major role of epinephrine in mediating stress-induced immune cell count increases and of epinephrine, renin, and blood volume changes in mediating subsequent immune cell count decreases from +1 min to +10 min after psychosocial stress cessation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Biological Activity of Fucoidan and Laminarin as Bioactive Polysaccharides from Irish Brown Macroalgae.","authors":"Shanmugapriya Karuppusamy, Janith Wanigasekara, Stephen Fitzpatrick, Henry Lyons, James Curtin, Gaurav Rajauria, Brijesh K Tiwari, Colm O'Donnell","doi":"10.3390/cells13231938","DOIUrl":"https://doi.org/10.3390/cells13231938","url":null,"abstract":"<p><p>This study aimed to investigate the biological activity of crude and purified laminarin and fucoidan samples extracted from Irish brown macroalgae species <i>Laminaria digitata</i> and <i>Fucus vesiculosus</i>. The antioxidant capacity of the samples was evaluated using the 2,2-diphenyl-1-picrylhydrazyl and ferric-reducing antioxidant power assays. The anti-inflammatory potential of the samples was analysed using the cyclooxygenases inhibition activity, and the antidiabetic activity was evaluated using a dipeptidyl peptidase-4 inhibitor screening assay. The cytotoxicity of the samples was measured using the Alamar Blue™ assay with different types of cancer cell lines. The crude laminarin and fucoidan samples exhibited higher antioxidant activity (<i>p</i> < 0.05) than the purified samples and commercial standards. Similarly, the crude extracts showed stronger anti-inflammatory and antidiabetic effects compared to the purified samples. Additionally, the crude laminarin and fucoidan samples showed higher cytotoxic activity. Specifically, as confirmed in the flow cytometry analysis, 3D tumour spheres using different cancer cell lines showed significantly higher resistance to bioactive compounds compared to 2D monolayer cells. The laminarin and fucoidan polysaccharide samples investigated are suitable for potential nutraceutical applications based on the biological activity values observed. Future research is necessary to purify the bioactive compounds investigated and improve their selectivity for targeted therapeutic uses in food and biomedical applications.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for a Role of the Long Non-Coding RNA ITGB2-AS1 in Eosinophil Differentiation and Functions.","authors":"Timothée Fettrelet, Aref Hosseini, Jacqueline Wyss, Joanna Boros-Majewska, Darko Stojkov, Shida Yousefi, Hans-Uwe Simon","doi":"10.3390/cells13231936","DOIUrl":"https://doi.org/10.3390/cells13231936","url":null,"abstract":"<p><p>Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (<i>ITGB2-AS1</i>) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable <i>ITGB2-AS1</i> knockdown in the HL-60 cell line. Interestingly, <i>ITGB2-AS1</i> deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, <i>ITGB2-AS1</i>-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that <i>ITGB2-AS1</i> plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Physical Activity on Cellular Metabolism Across Both Neurodegenerative and General Neurological Conditions: A Narrative Review.","authors":"Vicente Javier Clemente-Suárez, Alejandro Rubio-Zarapuz, Pedro Belinchón-deMiguel, Ana Isabel Beltrán-Velasco, Alexandra Martín-Rodríguez, José Francisco Tornero-Aguilera","doi":"10.3390/cells13231940","DOIUrl":"10.3390/cells13231940","url":null,"abstract":"<p><strong>Background: </strong>Regular physical activity plays a crucial role in modulating cellular metabolism and mitigating the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Multiple Sclerosis.</p><p><strong>Objective: </strong>The objective of this review is to evaluate the molecular mechanisms by which exercise influences cellular metabolism, with a focus on its potential as a therapeutic intervention for neurological disorders.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using peer-reviewed scientific articles, with a focus on the period between 2015 and 2024, to analyze the effects of exercise on mitochondrial function, oxidative stress, and metabolic health.</p><p><strong>Results: </strong>The findings indicate that exercise promotes mitochondrial biogenesis, enhances oxidative phosphorylation, and reduces reactive oxygen species, contributing to improved energy production and cellular resilience. These metabolic adaptations are associated with delayed disease progression and reduced symptoms in patients with neurodegenerative conditions. Additionally, integrating exercise with nutritional strategies may further enhance therapeutic outcomes by addressing metabolic disturbances comprehensively.</p><p><strong>Conclusions: </strong>This review concludes that personalized exercise protocols should be developed to optimize metabolic benefits for patients with neurological diseases, while future research should focus on biomarker development for individualized treatment approaches. These findings highlight the importance of non-pharmacological interventions in managing neurodegenerative diseases.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Immunoresponse in Bladder Cancer Immunotherapy.","authors":"Inmaculada Ruiz-Lorente, Lourdes Gimeno, Alicia López-Abad, Pedro López Cubillana, Tomás Fernández Aparicio, Lucas Jesús Asensio Egea, Juan Moreno Avilés, Gloria Doñate Iñiguez, Pablo Luis Guzmán Martínez-Valls, Gerardo Server, José Félix Escudero-Bregante, Belén Ferri, José Antonio Campillo, Eduardo Pons-Fuster, María Dolores Martínez Hernández, María Victoria Martínez-Sánchez, Diana Ceballos, Alfredo Minguela","doi":"10.3390/cells13231937","DOIUrl":"https://doi.org/10.3390/cells13231937","url":null,"abstract":"<p><p>Bladder cancer (BC) represents a wide spectrum of diseases, ranging from recurrent non-invasive tumors to advanced stages that require intensive treatments. BC accounts for an estimated 500,000 new cases and 200,000 deaths worldwide every year. Understanding the biology of BC has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to BC, immunotherapy with bacillus <i>Calmette-Guérin</i> (BCG) remains the gold standard in high-risk non-muscle invasive BC. For muscle-invasive BC and metastatic stages, immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have emerged as potent therapies, enhancing immune surveillance and tumor cell elimination. This review aims to unravel the immune responses involving innate and adaptive immune cells in BC that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Small Molecules to Reprogram RPE Cells in Regenerative Medicine for Degenerative Eye Disease.","authors":"Lyubov A Rzhanova, Elena V Alpeeva, Maria A Aleksandrova","doi":"10.3390/cells13231931","DOIUrl":"10.3390/cells13231931","url":null,"abstract":"<p><p>The main purpose of regenerative medicine for degenerative eye diseases is to create cells to replace lost or damaged ones. Due to their anatomical, genetic, and epigenetic features, characteristics of origin, evolutionary inheritance, capacity for dedifferentiation, proliferation, and plasticity, mammalian and human RPE cells are of great interest as endogenous sources of new photoreceptors and other neurons for the degrading retina. Promising methods for the reprogramming of RPE cells into retinal cells include genetic methods and chemical methods under the influence of certain low-molecular-weight compounds, so-called small molecules. Depending on the goal, which can be the preservation or the replacement of lost RPE cells and cellular structures, various small molecules are used to influence certain biological processes at different levels of cellular regulation. This review discusses the potential of the chemical reprogramming of RPE cells in comparison with other somatic cells and induced pluripotent stem cells (iPSCs) into neural cells of the brain and retina. Possible mechanisms of the chemically induced reprogramming of somatic cells under the influence of small molecules are explored and compared. This review also considers other possibilities in using them in the treatment of retinal degenerative diseases based on the protection, preservation, and support of survived RPE and retinal cells.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 23","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}