Cells最新文献

{"title":"GATAD2B O-GlcNAcylation Regulates Breast Cancer Stem-like Potential and Drug Resistance.","authors":"Giang Le Minh, Jessica Merzy, Emily M Esquea, Nusaiba N Ahmed, Riley G Young, Ryan J Sharp, Tejsi T Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer R Bethard, Susana Comte-Walters, Lauren E Ball, Mauricio J Reginato","doi":"10.3390/cells14060398","DOIUrl":"10.3390/cells14060398","url":null,"abstract":"<p><p>The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression of self-renewal factors and CSCs population. O-GlcNAcylation of GATAD2B at the C-terminus protects GATAD2B from ubiquitination and proteasomal degradation in breast cancer cells. We identify ITCH as a novel E3 ligase for GATAD2B and show that targeting ITCH genetically increases GATAD2B levels and increases CSCs phenotypes. Lastly, we show that overexpression of wild-type GATAD2B, but not the mutant lacking C-terminal O-GlcNAc sites, promotes mammosphere formation, expression of CSCs factors and drug resistance. Together, we identify a key role of GATAD2B and ITCH in regulating CSCs in breast cancer and GATAD2B O-GlcNAcylation as a mechanism regulating breast cancer stem-like populations and promoting chemoresistance.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708784","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}

{"title":"The Effects of Electrical Stimulation on a 3D Osteoblast Cell Model.","authors":"Crystal O Mahadeo, Alireza Shahin-Shamsabadi, Maedeh Khodamoradi, Margaret Fahnestock, Ponnambalam Ravi Selvaganapathy","doi":"10.3390/cells14060396","DOIUrl":"10.3390/cells14060396","url":null,"abstract":"<p><p>Electrical stimulation has been used with tissue engineering-based models to develop three-dimensional (3D), dynamic, research models that are more physiologically relevant than static two-dimensional (2D) cultures. For bone tissue, the effect of electrical stimulation has focused on promoting healing and regeneration of tissue to prevent bone loss. However, electrical stimulation can also potentially affect mature bone parenchymal cells such as osteoblasts to guide bone formation and the secretion of paracrine or endocrine factors. Due to a lack of physiologically relevant models, these phenomena have not been studied in detail. In vitro electrical stimulation models can be useful for gaining an understanding of bone physiology and its effects on paracrine tissues under different physiological and pathological conditions. Here, we use a 3D, dynamic, in vitro model of bone to study the effects of electrical stimulation conditions on protein and gene expression of SaOS-2 human osteosarcoma osteoblast-like cells. We show that different stimulation regimens, including different frequencies, exposure times, and stimulation patterns, can have different effects on the expression and secretion of the osteoblastic markers alkaline phosphatase and osteocalcin. These results reveal that electrical stimulation can potentially be used to guide osteoblast gene and protein expression.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708849","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}

{"title":"Association Between Synovial NTN4 Expression and Pain Scores, and Its Effects on Fibroblasts and Sensory Neurons in End-Stage Knee Osteoarthritis.","authors":"Ayumi Tsukada, Yui Uekusa, Etsuro Ohta, Akito Hattori, Manabu Mukai, Dai Iwase, Jun Aikawa, Yoshihisa Ohashi, Gen Inoue, Masashi Takaso, Kentaro Uchida","doi":"10.3390/cells14060395","DOIUrl":"10.3390/cells14060395","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic joint disease marked by synovial inflammation, cartilage degradation, and persistent pain. Although Netrin-4 (NTN4) has been implicated in pain modulation in rheumatoid arthritis (RA), its role in OA pain remains less understood. Previous research has documented that NTN4 promotes axonal growth in rodent-derived neurons; however, its effects on human sensory neurons are yet to be fully explored. NTN4 also plays a multifactorial role in various non-neuronal cells, such as endothelial cells, tumor cells, and stromal cells. Nevertheless, its specific impact on synovial fibroblasts, which are key components of the synovium and have been linked to OA pain, is still unclear. This study examined the correlation between NTN4 expression levels and pain severity in OA, specifically investigating its effects on human iPSC-derived sensory neurons (iPSC-SNs) and synovial fibroblasts from OA patients. Our findings indicate a positive correlation between synovial <i>NTN4</i> expression and pain severity. Recombinant human Netrin-4 (rh-NTN4) was also shown to enhance neurite outgrowth in human iPSC-SNs, suggesting a potential role in neuronal sensitization. Additionally, rh-NTN4 stimulated the production of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CXCL1, CXCL6, CXCL8) in synovium-derived fibroblastic cells, implicating it in synovial inflammation. Collectively, these results suggest that NTN4 may contribute to KOA pathology by promoting synovial inflammation and potentially sensitizing sensory neurons, thereby influencing the mechanisms of underlying pain.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708720","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}

{"title":"Chloroquine Causes Aging-like Changes in Diaphragm Neuromuscular Junction Morphology in Mice.","authors":"Chloe I Gulbronson, Sepideh Jahanian, Heather M Gransee, Gary C Sieck, Carlos B Mantilla","doi":"10.3390/cells14060390","DOIUrl":"10.3390/cells14060390","url":null,"abstract":"<p><p>Autophagy impairments have been implicated in various aging conditions. Previous studies in cervical motor neurons show an age-dependent increase in the key autophagy proteins LC3 and p62, reflecting autophagy impairment and autophagosome accumulation. Chloroquine is commonly used to inhibit autophagy by preventing autophagosome-lysosome fusion and may thus emulate the effects of aging on the neuromuscular system. Indeed, acute chloroquine administration in old mice decreases maximal transdiaphragmatic pressure generation, consistent with aging effects. We hypothesized that chloroquine alters diaphragm muscle neuromuscular junction (NMJ) morphology and increases denervation. Adult male and female C57BL/6 × 129J mice between 5 and 8 months of age were used to examine diaphragm muscle NMJ morphology and denervation following daily intraperitoneal injections of chloroquine (10 mg/kg/d) or vehicle for 7 days. The motor end-plates and pre-synaptic terminals were fluorescently labeled with α-bungarotoxin and anti-synaptophysin, respectively. Confocal microscopy was used to assess pre- and post-synaptic morphology and denervation. At diaphragm NMJs, chloroquine treatment decreased pre-synaptic volume by 12% compared to the vehicle (<i>p</i> < 0.05), with no change in post-synaptic volume. Chloroquine treatment increased the proportion of partially denervated NMJs by 2.7-fold compared to vehicle treatment (<i>p</i> < 0.05). The morphological changes observed were similar to those previously reported in the diaphragm muscles of 18-month-old mice. These findings highlight the importance of autophagy in the maintenance of the structural properties at adult NMJs in vivo.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708673","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}

{"title":"Adaptive Thermogenesis and Lipid Metabolism Modulation in Inguinal and Perirenal Adipose Tissues of <i>Hezuo Pigs</i> in Response to Low-Temperature Exposure.","authors":"Yao Li, Hai-Xia Shi, Jie Li, Hong Du, Rui Jia, Yu-Hao Liang, Xiao-Yu Huang, Xiao-Li Gao, Shuang-Bao Gun, Qiao-Li Yang","doi":"10.3390/cells14060392","DOIUrl":"10.3390/cells14060392","url":null,"abstract":"<p><p>In mammals, exposure to low temperatures induces white adipose tissue (WAT) browning and alters lipid metabolism to promote thermogenesis, thereby maintaining body temperature. However, this response varies across different adipose depots. In this study, <i>Hezuo pigs</i> were exposed to either room temperature (23 ± 2 °C) or low temperature (-15 ± 2 °C) for periods of 12 h, 24 h, 48 h, 5 d, 10 d, and 15 d. Inguinal fat (IF) and perirenal fat (PF) were collected and analyzed using hematoxylin and eosin (HE) staining, transmission electron microscopy, RT-qPCR, and RNA-seq. Following cryoexposure, our results demonstrated a significant increase in adipocyte number and a corresponding decrease in cross-sectional area in both IF and PF groups from 24 h to 10 d. While adipocyte numbers were elevated at 12 h and 15 d, these changes were not statistically significant. Moreover, lipid droplets and mitochondria were more abundant, and the mRNA expression levels of thermogenic genes <i>UCP3</i> and <i>PGC-1α</i> were significantly higher compared to the control group during the 24 h-10 d cold exposure period. No significant changes were observed in the other groups. RNA-seq data indicated that the lipid metabolism of IF and PF peaked on day 5 of low-temperature treatment. In IF tissue, lipid metabolism is mainly regulated by genes such as <i>FABP4</i>, <i>WNT10B</i>, <i>PCK1</i>, <i>PLIN1</i>, <i>LEPR</i>, and <i>ADIPOQ</i>. These genes are involved in the classical lipid metabolism pathway and provide energy for cold adaptation. In contrast, in PF tissue, genes like <i>ATP5F1A</i>, <i>ATP5PO</i>, <i>SDHB</i>, <i>NDUFS8</i>, <i>SDHA</i>, and <i>COX5A</i> play roles within the neurodegenerative disease pathway, and PF tissue has a positive impact on the process related to degenerative diseases. Further investigation is needed to clarify the functions of these candidate genes in lipid metabolism in <i>Hezuo pigs</i> and to explore the genetic mechanisms underlying the cold-resistance traits in local pig populations.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708606","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}

{"title":"Epigallocatechin Gallate Promotes Cuproptosis via the MTF1/ATP7B Axis in Hepatocellular Carcinoma.","authors":"Yuhan Fu, Lirui Hou, Kai Han, Chong Zhao, Hongbo Hu, Shutao Yin","doi":"10.3390/cells14060391","DOIUrl":"10.3390/cells14060391","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis is a form of copper-dependent non-apoptotic cell death. Cancer cells that prefer to use aerobic glycolysis for energy generation are commonly insensitive to cuproptosis, which hinders its application for cancer treatment. Epigallocatechin gallate (EGCG) possesses diverse pharmacological activities. However, the association between EGCG and cuproptosis has not been studied.</p><p><strong>Methods: </strong>The cell viability, proliferation, and cuproptosis-related protein levels were detected to investigate whether EGCG enhances the sensitivity of HCC cells to cuproptosis. The intracellular copper level, related copper metabolism proteins, and gene expression were detected to explore the mechanisms. In addition, a nude mouse xenograft model was established to determine the effects of EGCG on cuproptosis in tumor tissues.</p><p><strong>Results: </strong>The combination of EGCG and copper ionophores significantly enhanced the mortality of HCC cells and heightened the sensitivity of HCC cells to cuproptosis. There was a notable reduction in the expression of copper export protein copper-transporting P-type ATPase (ATP7B). EGCG effectively suppressed metal regulatory transcription factor (MTF1) expression and subsequently hindered the transcriptional regulation of ATP7B. EGCG also facilitated the intratumoral accumulation of copper and augmented susceptibility to cuproptosis in vivo.</p><p><strong>Conclusions: </strong>EGCG can increase the sensitivity of hepatocellular carcinoma cells to cuproptosis by promoting intracellular copper accumulation through the MTF1/ATP7B axis.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708775","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}

{"title":"Anti-Tumor Effects of Cecropin A and Drosocin Incorporated into Macrophage-like Cells Against Hematopoietic Tumors in <i>Drosophila mxc</i> Mutants.","authors":"Marina Hirata, Tadashi Nomura, Yoshihiro H Inoue","doi":"10.3390/cells14060389","DOIUrl":"10.3390/cells14060389","url":null,"abstract":"<p><p>Five major antimicrobial peptides (AMPs) in <i>Drosophila</i> are induced in <i>multiple sex combs</i> (<i>mxc</i>) mutant larvae harboring lymph gland (LG) tumors, and they exhibit anti-tumor effects. The effects of other well-known AMPs, Cecropin A and Drosocin, remain unexplored. We investigated the tumor-elimination mechanism of these AMPs. A half-dose reduction in either the <i>Toll</i> or <i>Imd</i> gene reduced the induction of these AMPs and enhanced tumor growth in <i>mxc^mbn1</i> mutant larvae, indicating that their anti-tumor effects depend on the innate immune pathway. Overexpression of these AMPs in the fat body suppressed tumor growth without affecting cell proliferation. Apoptosis was promoted in the mutant but not in normal LGs. Conversely, knockdown of them inhibited apoptosis and enhanced tumor growth; therefore, they inhibit LG tumor growth by inducing apoptosis. The AMPs from the fat body were incorporated into the hemocytes of mutant but not normal larvae. Another AMP, Drosomycin, was taken up via phagocytosis factors. Enhanced phosphatidylserine signals were observed on the tumor surface. Inhibition of the signals exposed on the cell surface enhanced tumor growth. AMPs may target phosphatidylserine in tumors to induce apoptosis and execute their tumor-specific effects. AMPs could be beneficial anti-cancer drugs with minimal side effects for clinical development.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708718","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}

{"title":"Mechanism of β-Catenin in Pulmonary Fibrosis Following SARS-CoV-2 Infection.","authors":"Min Jiang, Jiaqi Hou, Qianqian Chai, Shihao Yin, Qian Liu","doi":"10.3390/cells14060394","DOIUrl":"10.3390/cells14060394","url":null,"abstract":"<p><p>Pulmonary fibrosis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of death in patients with COVID-19. β-catenin, a key molecule in the Wnt/β-catenin signaling pathway, has been shown to be involved in the development of pulmonary fibrosis (e.g., idiopathic pulmonary fibrosis, silicosis). In this study, we developed a SARS-CoV-2-infected A549-hACE2 cell model to evaluate the efficacy of the A549-hACE2 monoclonal cell line against SARS-CoV-2 infection. The A549-hACE2 cells were then subjected to either knockdown or overexpression of the effector β-catenin, and the modified cells were subsequently infected with SARS-CoV-2. Additionally, we employed transcriptomics and raw letter analysis approaches to investigate other potential effects of β-catenin on SARS-CoV-2 infection. We successfully established a model of cellular fibrosis induced by SARS-CoV-2 infection in lung-derived cells. This model can be utilized to investigate the molecular biological mechanisms and cellular signaling pathways associated with virus-induced lung fibrosis. The results of our mechanistic studies indicate that β-catenin plays a significant role in lung fibrosis resulting from SARS-CoV-2 infection. Furthermore, the inhibition of β-catenin mitigated the accumulation of mesenchymal stroma in A549-hACE2 cells. Additionally, β-catenin knockdown was found to facilitate multi-pathway crosstalk following SARS-CoV-2 infection. The fact that β-catenin overexpression did not exacerbate cellular fibrosis may be attributed to the activation of PPP2R2B.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708501","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}

{"title":"Role of Galactosylceramide Metabolism in Satellite Glial Cell Dysfunction and Neuron-Glia Interactions in Painful Diabetic Peripheral Neuropathy.","authors":"Xin Xu, Yue Zhang, Shuo Li, Chenlong Liao, Xiaosheng Yang, Wenchuan Zhang","doi":"10.3390/cells14060393","DOIUrl":"10.3390/cells14060393","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is a prevalent and disabling complication of diabetes, with painful diabetic peripheral neuropathy (PDPN) being its most severe subtype due to chronic pain and resistance to treatment. Satellite glial cells (SGCs), critical for maintaining dorsal root ganglion (DRG) homeostasis, undergo significant structural and functional changes under pathological conditions. This study investigated the role of galactosylceramide (GalCer), a key sphingolipid, in SGC dysfunction and neuron-glia interactions during DPN progression. Using a rat model of PDPN, we employed single-cell RNA sequencing (scRNA-seq), targeted mass spectrometry, and immunofluorescence analysis. The PDPN group exhibited transcriptional activation and structural reorganization of SGCs, characterized by increased SGC abundance and glial activation, evidenced by elevated Gfap expression. Functional enrichment analyses revealed disruptions in sphingolipid metabolism, including marked reductions in GalCer levels. Subclustering identified vulnerable SGC subsets, such as Cluster a, with dysregulated lipid metabolism. The depletion of GalCer impaired SGC-neuron communication, destabilizing DRG homeostasis and amplifying neurodegeneration and neuropathic pain. These findings demonstrate that GalCer depletion is a central mediator of SGC dysfunction in PDPN, disrupting neuron-glia interactions and exacerbating neuropathic pain. This study provides novel insights into the molecular mechanisms of DPN progression and identifies GalCer metabolism as a potential therapeutic target.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708805","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}

{"title":"Insights into the Roles of GLP-1, DPP-4, and SGLT2 at the Crossroads of Cardiovascular, Renal, and Metabolic Pathophysiology.","authors":"Melania Gaggini, Laura Sabatino, Adrian Florentin Suman, Kyriazoula Chatzianagnostou, Cristina Vassalle","doi":"10.3390/cells14050387","DOIUrl":"10.3390/cells14050387","url":null,"abstract":"<p><p>In recent years, new drugs for the treatment of type 2 diabetes (T2D) have been proposed, including glucagon-like peptide 1 (GLP-1) agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Over time, some of these agents (in particular, GLP-1 agonists and SGLT2 inhibitors), which were initially developed for their glucose-lowering actions, have demonstrated significant beneficial pleiotropic effects, thus expanding their potential therapeutic applications. This review aims to discuss the mechanisms, pleiotropic effects, and therapeutic potential of GLP-1, DPP-4, and SGLT2, with a particular focus on their cardiorenal benefits beyond glycemic control.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604194","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}