Experimental Animals最新文献

{"title":"Differential regulation of K⁺-Cl^- cotransporter 2 (KCC2) and Na⁺-K⁺-Cl^- cotransporter 1 (NKCC1) expression by zolpidem in CA1 and CA3 hippocampal subregions of the lithium-pilocarpine status epilepticus rat model.","authors":"Muhammad Zulfadhli Othman, Mohd Hamzah Mohd Nasir, Wan Amir Nizam Wan Ahmad, Jafri Malin Abdullah, Ahmad Tarmizi Che Has","doi":"10.1538/expanim.24-0120","DOIUrl":"10.1538/expanim.24-0120","url":null,"abstract":"<p><p>Status epilepticus is linked to cognitive decline due to damage to the hippocampus, a key structure involved in cognition. The hippocampus's high vulnerability to epilepsy-related damage is the main reason for this impairment. Convulsive seizures, such as those observed in status epilepticus, can cause various hippocampal pathologies, including inflammation, abnormal neurogenesis, and neuronal death. Interestingly, substantial evidence points to the therapeutic potential of the sedative/hypnotic agent zolpidem for neurorehabilitation in brain injury patients, following the unexpected discovery of its paradoxical awakening effect. In this study, we successfully established an ideal lithium-pilocarpine rat model of status epilepticus, which displayed significant deficits in hippocampal-dependent learning and memory. The Morris water maze test was used to assess zolpidem's potential to improve learning and memory, as well as its impact on anxiety-like behavior and motor function. Immunohistochemical staining and fluorescence analysis were used to examine the effect of zolpidem on K⁺-Cl^- cotransporter 2 (KCC2) and Na⁺-K⁺-Cl^- cotransporter 1 (NKCC1) protein expression in the hippocampal CA1 and CA3. Our findings showed that zolpidem did not improve learning and memory in status epilepticus rats. Additionally, its sedative/hypnotic effects were not apparent in the status epilepticus condition. However, immunohistochemical results revealed that zolpidem significantly restored altered NKCC1 levels in the CA1 and CA3 to levels similar to those seen in normal rats. These findings suggest that zolpidem may contribute to molecular restoration, particularly through its impact on NKCC1 protein expression in the hippocampus, which is crucial for proper inhibitory neurotransmission in the brain.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"286-299"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological characteristics of age-related changes in C57BL/6 mice sub-strains in the national center for geriatrics and gerontology aging farm.","authors":"Noboru Ogiso, Julio A Almunia, Yoshiko Munesue, Shunsuke Yuri, Akihiko Nishikimi, Atsushi Watanabe, Morihiro Inui, Kazumichi Takano, Shumpei Niida","doi":"10.1538/expanim.24-0095","DOIUrl":"10.1538/expanim.24-0095","url":null,"abstract":"<p><p>Aging is a complex biological process. Several animal models, including nematodes, Drosophila, and rodents, have been used in research on aging mechanisms and the extension of healthy life expectancy. The present study investigated the physiological and anatomical changes associated with aging in two sub-strains of aged C57BL/6 mice used in aging research: C57BL/6NCrSlc (B6N) and C57BL/6J (B6J). The survival rate before 24 months old (mo) was higher in B6J mice than in B6N mice; however, after 24 mo, it was markedly lower in the former than in the latter. Body weight increased in male C57BL/6 mice until 15-18 mo and in females until 21-24 mo and then began to decrease. Body temperature was lower in B6N mice than in B6J mice until 24 mo. Food and water intakes increased from 18 mo in both strains. The incidence of alopecia was higher in female C57BL/6J mice from 3 mo. Necropsy findings showed a high rate of spontaneous tumors in both sub-strains. The incidence of cutaneous ulcerative infections and hepatic pathologies was significantly higher in the B6N strain. A high incidence of renal lesions was also observed in B6J mice, particularly in males. These results provide insights into the characteristics of these sub-strains and the phenotypic changes associated with aging, which will facilitate the use of aged mice as a quality resource for geriatric and gerontological research.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"229-238"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics and metabolomics analysis of the pathogenesis of a novel hyperlipidemia-susceptible rat strain.","authors":"Xiufeng Ai, Qian Zhang, Quanxin Ma, Mingsun Fang, Keyan Zhu, Yueqin Cai, Qinqin Yang, Lizong Zhang","doi":"10.1538/expanim.24-0080","DOIUrl":"10.1538/expanim.24-0080","url":null,"abstract":"<p><p>Wistar-SD Hypercholesterolemia (WSHc) Rat is a novel hyperlipidemia-susceptible rat that we discovered and bred earlier, which can be used as an ideal animal model for the study of non-alcoholic fatty liver disease (NAFLD). However, its pathogenesis of hyperlipidemia and genetic and biological characteristics need to be further investigated. In the current study, WSHc rats were fed a high-fat diet (HFD) and standard chow (SC), with age-matched Wistar rats as the control group undergoing the same treatment, followed by serum lipid level measurement. It was found that HFD-fed WSHc rats developed dyslipidemia. Transcriptomic analysis was performed to detect genes associated with cholesterol metabolism in the liver, and 119 differentially expressed genes were discovered through bioinformatics analysis and molecular biology verification. Additionally, Srebf1 was identified as a HUB gene and Nr1d1 as an independent key gene using the protein-protein interaction network and one-cluster clustering analysis. The two genes had also been further validated in molecular biology experiments and were consistent with transcriptomic results. Serum lipid metabolomics analysis identified 7 lipid subclasses and 84 lipid molecules using UHPLC-Q-TOF/MS. There were 62 and 70 lipid molecules with significant differences in the metabolic profiles of serum lipid mediators in the WSHc+HFD group compared to the WSHc+SC and Wistar+HFD groups, respectively, and the differential metabolites were mainly produced via sphingolipid and glycerophospholipid metabolism. In sum, the hypercholesterolemia model can be established with WSHc rats after the HFD induction, and the pathogenesis involves the Srebf1 and Nr1d1 genes and the sphingolipid and glycerophospholipid metabolism pathways.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"160-172"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice.","authors":"Yuta Seki, Shumpei P Yasuda, Xuehan Hou, Kayoko Tahara, Ornjira Prakhongcheep, Ai Takahashi, Yuki Miyasaka, Hirohide Takebayashi, Yoshiaki Kikkawa","doi":"10.1538/expanim.24-0141","DOIUrl":"10.1538/expanim.24-0141","url":null,"abstract":"<p><p>An unconventional myosin, myosin VI gene (MYO6), contributes to recessive and dominant hearing loss in humans and mice. The Kumamoto shaker/waltzer (ksv) mouse is a model of deafness resulting from a splice-site mutation in Myo6. While ksv/ksv homozygous mice are deaf due to cochlear hair cell stereocilia fusion at the neonatal stage, the hearing phenotypes of ksv/+ heterozygous mice have been less clear. Due to this splicing error, most MYO6 protein expression is lost in ksv mice; however, MYO6 with a single amino acid mutation (p.E461K) remains expressed. In this study, we investigated the hearing phenotypes and effect of a p.E461K mutation in ksv/+ heterozygous mice. Hearing tests indicated that hearing loss in ksv/+ mice arises concurrently at both low and high frequencies. In the low-frequency region, stereocilia fusions were detected in the inner hair cells of ksv/+ mice. Expression analysis revealed abnormal MYO6 expression and localization, along with atypical expression of proteins in the basal region of the stereocilia, suggesting that these abnormalities may contribute to stereocilia fusion in ksv/+ mice. Conversely, although the expression patterns of MYO6 and stereociliary basal-region proteins appeared normal in the cochlear area corresponding to high-frequency sounds, stereocilia loss in the outer hair cells was observed in ksv/+ mice. These findings suggest that the ksv/+ mice exhibit distinct mechanisms underlying hearing loss across areas responsible for low- and high-frequency hearing, differing from those previously reported in heterozygous Myo6 mice with loss-of-function and missense mutant alleles.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"251-263"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA repair protein RAD50 is involved in the streptozotocin-induced diabetes susceptibility of mice.","authors":"Yuki Miyasaka, Tomoki Maegawa, Takuma Nagura, Misato Kobayashi, Naru Babaya, Hiroshi Ikegami, Fumihiko Horio, Tamio Ohno","doi":"10.1538/expanim.24-0071","DOIUrl":"10.1538/expanim.24-0071","url":null,"abstract":"<p><p>Streptozotocin (STZ) is widely used as a pancreatic beta-cell toxin to induce experimental diabetes in rodents. Strain-dependent variations in STZ-induced diabetes susceptibility have been reported in mice. Differences in STZ-induced diabetes susceptibility are putatively related to pancreatic beta-cell fragility via DNA damage response. In this study, we identified two STZ-induced diabetes susceptibility regions in chromosome 11 (Chr11) of Nagoya-Shibata-Yasuda (NSY) mice via congenic mapping using the C3H-11^NSY consomic strains, in which the entire Chr11 of STZ-resistant C3H/He (C3H) mice was replaced with that of NSY mice, and named them STZ susceptibility region for NSY (Ssnsy)-1 and -2, respectively. Screening for variants in the Ssnsy1 region revealed that NSY mice exhibited a characteristic missense c.599G>T (p.G200V) variant in a highly conserved region within the DNA repair gene, RAD50 double-strand break repair protein (Rad50). Subsequently, we generated R2B1-Rad50 knock-in mice, in which c.599T in Rad50 of STZ-susceptible C3H.NSY-R2B1 subcongenic mice was replaced with c.599G via genome editing. Compared with C3H.NSY-R2B1 mice, and R2B1-Rad50 knock-in mice showed suppressed hyperglycemia, incidence of diabetes, and decrease in plasma insulin levels following single high-dose and multiple low-dose injections of STZ. Our results suggest Rad50 as a susceptibility gene for STZ-induced diabetes that is involved in pancreatic beta-cell fragility. Forward genetic approaches using inbred mouse strains with STZ susceptibility as a phenotypic indicator will further elucidate the molecular mechanisms of pancreatic beta-cell destruction via DNA damage response.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"264-275"},"PeriodicalIF":2.2,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acot1 overexpression alleviates heart failure by inhibiting oxidative stress and cardiomyocyte apoptosis through the Keap1-Nrf2 pathway.","authors":"Xiaolu Hou, Guoling Hu, Heling Wang, Ying Yang, Qi Sun, Xiuping Bai","doi":"10.1538/expanim.24-0129","DOIUrl":"https://doi.org/10.1538/expanim.24-0129","url":null,"abstract":"<p><p>Heart failure (HF) is a clinical syndrome related to multiple causes, including oxidative stress. Acyl-CoA thioesterase 1 (Acot1) is an enzyme in fatty acids metabolism, but it remains unclear in HF. Transverse aortic coarctation induced HF mouse model and hypoxia-stimulated cardiomyocyte (HL-1) model were established. Acot1 expression was down-regulated in heart tissues of HF mice. AAV9-mediated Acot1 overexpression improved cardiac function and pathological injury of heart tissues in TAC-induced HF mice. Acot1 overexpression ameliorated oxidative stress in heart tissues of HF mice and hypoxia-stimulated HL-1 cells, as indicated by reduced ROS and MDA levels and elevated SOD and GSH levels. We found that Acot1 overexpression inhibited apoptosis both in vivo and in vitro, with decreased protein levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Mechanically, Acot1 activated Keap1-Nrf2 pathway, leading to the nuclear translocation of Nrf2 and increased Nrf2-regulated gene NQO1 expression. Rescue experiment indicated that ML385 (Nrf2 inhibitor) abolished the effect of Acot1 overexpression on oxidative stress. Collectively, these results suggested that Acot1 overexpression protects heart from injury by inhibiting oxidative stress and apoptosis, possibly through activating Keap1-Nrf2 pathway.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-route medetomidine-alfaxalone-butorphanol anesthesia: a refined protocol for balanced anesthesia in male rabbits.","authors":"Risa Iwanaga, Munekatsu Ita, Kanako Sumi, Chizuko Kodama, Mohammad Ibrahim Qasimi, Jun Tamura, Ko Nakanishi, Kayoko Matsumura, Masami Morimatsu, Yasuhiro Yoshida, Teppei Nakamura","doi":"10.1538/expanim.24-0151","DOIUrl":"https://doi.org/10.1538/expanim.24-0151","url":null,"abstract":"<p><p>Injectable anesthesia is widely used in laboratory animals because of its ease of administration and minimal equipment requirements. However, it necessitates careful monitoring as well as thermal and oxygen support. This study evaluated the efficacy of medetomidine-alfaxalone-butorphanol (MAB) anesthesia in male rabbits using a dual-route administration protocol. The anesthetic doses were as follows: medetomidine, 0.2 mg/kg; alfaxalone, 2.0 mg/kg; and butorphanol, 2.0 mg/kg. MAB anesthesia, administered via intravenous and subcutaneous routes, induced rapid and smooth induction, achieving anesthetic scores comparable to those of medetomidine-midazolam-butorphanol (MMB) anesthesia. MAB anesthesia resulted in mild hypothermia during the procedure. Upon atipamezole administration, rabbits under MAB anesthesia exhibited faster recovery of the righting reflex and respiration rate than those under MMB. Importantly, no abnormal behaviors, such as jumping or agitation, were observed during induction or recovery, as reported with alfaxalone use in other species. Both protocols maintained spontaneous breathing, although transient hypoxemia was observed in all rabbits. The dual-route MAB protocol provided effective anesthesia while addressing the limitations of conventional MMB anesthesia in rabbits, suggesting its potential as a refined anesthetic method for this species. Unlike mice, which showed weaker anesthetic effects with MAB compared to MMB, MAB demonstrated superior anesthetic properties in rabbits. This study highlights the importance of species-specific anesthetic protocols and the potential benefits of MAB anesthesia in rabbits, particularly its smooth induction and recovery profile, without adverse behaviors often associated with alfaxalone in other species.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference intervals for hematologic and biochemical values in cynomolgus monkeys from different breeding populations in China.","authors":"Shuyan Wang, Yongtao Liu, Caiyun Li, Lei Shi, Qiao Zhao, Jiang Lv, Yuwen Zhang, Xijie Wang, Yan Chang","doi":"10.1538/expanim.24-0110","DOIUrl":"https://doi.org/10.1538/expanim.24-0110","url":null,"abstract":"<p><p>The cynomolgus monkey is the most widely used models in non-clinical studies. As factors like age, gender, and breeding province may affect hematologic and serum biochemical parameters, it is important to establish base values of these parameters by these three factors and to determine the effects of these factors on the parameters. In total, 1794 cynomolgus monkeys (Male: 901, Female: 893) were selected. A total of 24 hematologic and 21 serum biochemical parameters were measured, and the effects of age, gender, and breeding province were analyzed. Base values for hematologic and serum biochemical parameters were established by age, gender, and breeding province. A significant neutrophil percent, alkaline phosphatase, and creatinine differences were observed between different ages; a significant alkaline phosphatase, gamma glutamyl transpeptidase, and creatinine differences were observed between males and females; a significant lymphocyte percent, neutrophil percent, reticulocyte count, alkaline phosphatase, gamma glutamyl transpeptidase, and creatinine differences were observed between different breeding provinces. The results emphasize the importance of improving base values by age, gender, and breeding provinces. There was no statistically significant difference in most of the above parameters, and cynomolgus monkeys from different breeding provinces can be used in the same study.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.","authors":"Junxiang Yin, Jerelyn A Nick, Swati Khare, Heidi E Kloefkorn, Ming Gao, Michael Wu, Jennifer White, James L Resnick, Kyle D Allen, Harry S Nick, Michael F Waters","doi":"10.1538/expanim.24-0118","DOIUrl":"https://doi.org/10.1538/expanim.24-0118","url":null,"abstract":"<p><p>Spinocerebellar ataxia 13 (SCA13) is an autosomal dominant neurological disorder caused by mutations in KCNC3. Our previous studies revealed that KCNC3 (Potassium Voltage-Gated Channel Subfamily C Member 3)mutation R423H results in an early-onset form of SCA13. Previous biological models of SCA13 include zebrafish and Drosophila but no mammalian systems. More recently, mouse models with Kcnc3 mutations presented behavioral abnormalities but without obvious pathological changes in the cerebellum, a hallmark of patients with SCA13. Here, we present a novel transgenic mouse model by bacterial artificial chromosome (BAC) recombineering to express the full-length mouse Kcnc3 expressing the R424H mutation. This BAC-R424H mice exhibited behavioral and pathological changes mimicking the clinical phenotype of the disease. The BAC-R424H mice (homologous to R423H in human) developed early onset clinical symptoms with aberrant gait, tremor, and cerebellar atrophy. Histopathological analysis of the cerebellum in BAC-R424H mice showed progressive Purkinje cell loss and thinning of the molecular cell layer. Additionally, Purkinje cells of BAC-R424H mice showed significantly lower spontaneous firing frequency with a corresponding increase in inter-spike interval compared to that of wild-type mice. Our SCA13 transgenic mice recapitulate both neuropathological and behavioral changes manifested in human SCA13 R423H patients and provide an advantageous approach to understanding the role of voltage-gated potassium channel in cerebellar morphogenesis and function. This mammalian in vivo model will lead to further understanding of the R423H allelic form of SCA13 from the molecular to the behavioral level and serve as a platform for testing potential therapeutic compounds.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFRC knockdown attenuates atrial fibrillation by inhibiting cardiomyocyte ferroptosis and atrial fibrosis.","authors":"Yufei Zhan, Yang Zhou, Chi Zhang, Zongwang Zhai, Yi Yang, Xingpeng Liu","doi":"10.1538/expanim.24-0127","DOIUrl":"https://doi.org/10.1538/expanim.24-0127","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is a common arrhythmia in clinical. Its most important pathophysiological factor is atrial fibrosis. Transferrin receptor (TFRC) promotes ferroptosis by facilitating iron uptake. Its role in AF is unknown. TFRC expression in Angiotensin II (Ang II)-induced AF mice was significantly upregulated. TFRC knockdown significantly reduced AF occurrence. TFRC silence ameliorated myocardial fibrosis by inhibiting TGF-β1/Smad2 pathway in vivo. TFRC interference reduced ferroptosis by inhibiting lipid oxidation product generation in vivo. Ang II-induced HL-1 cardiomyocyte model was employed to simulate an in vivo situation. The in vitro results were consistent with the in vivo results. FOXO3 was reported to protect atrium against fibrosis and participate in ferroptosis. FOXO3 exerted transcriptional repressive activity by binding to TFRC promoter. FOXO3 overexpression protected HL-1 cells against ferroptosis, which was reversed by TFRC overexpression. In summary, TFRC knockdown reduces AF occurrence by ameliorating atrial fibrosis through inhibiting cardiomyocyte ferroptosis under FOXO3 regulation.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}