Molecular medicine reports最新文献

{"title":"Expression, immunogenicity and clinical significance analysis of thyroid‑stimulating hormone receptor fusion proteins.","authors":"Xia Chen, Hui Chen","doi":"10.3892/mmr.2025.13639","DOIUrl":"10.3892/mmr.2025.13639","url":null,"abstract":"<p><p>Thyroid function is regulated in a substantial manner by thyroid‑stimulating hormone receptor (TSHR), and aberrant alterations in thyroid function are triggered by the interaction of TSHR with its antibodies, thyroid‑stimulating hormone receptor antibodies (TRAb). The expression, immunogenicity and clinical significance of fusion proteins comprising different structural domains of TSHR were investigated. Fusion proteins containing several human TSHR (hTSHR) structural domains were created. <i>In vitro</i> experiments utilized these fusion proteins as antigens to specifically bind and analyze patient sera using an ELISA. To investigate the immunogenicity and clinical significance of various structural domains of TSHR, <i>in vivo</i> experiments included immunizing BALB/c mice with various fusion proteins of hTSHR, measuring serum autoantibodies, assessing thyroid function, performing histological examination and using flow cytometry to identify changes in T cell subsets. Three distinct hTSHR fusion protein fragments (hTSHR289, hTSHR290 and hTSHR410) were synthesized. The hTSHR290 fusion protein demonstrated the highest binding reaction with TRAb⁺ sera from patients with hypothyroidism, and the hTSHR289 fusion protein demonstrated considerable specific binding reactivity with stimulating antibodies, as observed in sera from patients with hyperthyroidism. Pathological alterations associated with hyperthyroidism were observed in mice in the hTSHR289 fusion protein group, while pathological changes associated with hypothyroidism were observed in mice in the hTSHR290 fusion protein group. Immunized BALB/c mice exhibited increased levels of CD4⁺ T cell subsets, and decreased levels of CD8⁺CD122⁺ and CD4⁺CD25⁺ T cell subsets. Fusion proteins of different structural domains of TSHR exhibited varying immunogenicity. The hTSHR289 fusion protein and hTSHR290 fusion protein prepared in the present study could serve as a basis for the development of ELISA kits for the detection of thyroid‑stimulating immunoglobulins and TSHR‑blocking antibodies. Fusion proteins of different structural domains of TSHR induced clinical symptoms of hyperthyroidism and hypothyroidism in mice. The present study provides a scientific basis for future studies on the etiology and mechanisms of autoimmune thyroid diseases, as well as the invention of novel methods for TRAb detection.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of obesity and estrogen deficiency in non‑alcoholic fatty liver disease: Insights from a mouse model.","authors":"Aaron Afonso-Alí, Jano Dicroce-Giacobini, Silvia Teixido-Trujillo, Esteban Porrini, José Antonio Pérez-Pérez, Sonia García-Hernández, Sergio Luis-Lima, Beatriz Abrante-Pérez, Alberto Hernández-Bustabad, Nieves Guadalupe Acosta-González, Miriam Iglesias-Hernández, Laura Díaz-Martín, Covadonga Rodríguez-González, Manuel Hernández-Guerra, Ana Elena Rodríguez-Rodríguez","doi":"10.3892/mmr.2025.13629","DOIUrl":"10.3892/mmr.2025.13629","url":null,"abstract":"<p><p>The prevalence of non‑alcoholic fatty liver disease (NAFLD) increases in post‑menopausal women, driven by obesity and metabolic syndrome (MS). However, the pathogenesis of this interaction remains poorly understood. The present study investigated the interplay between obesity, menopause and NAFLD in a C57BL6/J mouse model of diet‑induced obesity. The study included male and female animals, in which a subgroup of females underwent ovariectomy to simulate menopause. Mice were fed a high‑fat diet for 6 months which resulted in them becoming overweight, and developing hyperglycemia and insulin resistance. The present study analyzed liver histology, inflammatory markers and hepatic lipid profiles. All obese animals showed liver steatosis, hepatocyte ballooning and fibrosis. Sex‑related differences were observed, including: i) Obese male mice developed increased expression of inflammatory markers and altered lipid profile; ii) obese female mice exhibited less severe steatosis, hepatic inflammation and lipotoxicity, and iii) ovariectomized obese female mice exhibited exacerbated hepatic lipotoxicity and tissue damage. Ovariectomized obese female mice also had reduced triacylglycerol and cholesteryl ester levels, but increased levels of toxic intermediaries, such as free fatty acids, diacylglycerols and free cholesterol, elevated expression of NF‑κB in the liver and increased levels of serum transaminases, indicating liver damage. These findings suggested that estrogen may protect against NAFLD progression by regulating lipid droplet formation, especially in the context of insulin resistance. More studies in the field are clearly needed to achieve a complete understanding of these pathways, which may serve to improve current therapies.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12319388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts.","authors":"Jianjun Li, Dongzhen Zhu, Mengde Zhang, Zhao Li, Liting Liang, Yuyan Huang, Xu Guo, Yi Kong, Xiaobing Fu, Sha Huang","doi":"10.3892/mmr.2025.13643","DOIUrl":"10.3892/mmr.2025.13643","url":null,"abstract":"<p><p>Aging impairs wound healing, primarily because of alterations in cell phenotypes and interactions, particularly between endothelial cells (ECs) and fibroblasts (Fibs). The present study investigated the dynamics of EC‑Fib interactions in aged wounds using a mouse model and single‑cell transcriptomics, supplemented by CellChat analysis and functional validation using <i>in vitro</i> co‑culture systems. Aged mice exhibited markedly reduced wound healing efficiency and impaired angiogenesis when compared with younger mice, as indicated by hematoxylin and eosin and immunohistochemical staining. Single‑cell transcriptomic analysis revealed that the regeneration of ECs and Fibs was delayed in aged wounds. Furthermore, key genes involved in angiogenesis and tissue repair were downregulated, whereas those related to inflammation and aging were upregulated. Integrating CellChat analysis with <i>in vitro</i> co‑culture validation, it was found that the bidirectional communication between ECs and Fibs, predominantly mediated via the transforming growth factor β pathway, was markedly reduced in aged wounds. These findings underscored the critical role of disrupted cell‑cell communication in age‑related impaired wound healing, providing mechanistic evidence for potential therapeutic strategies to enhance wound healing in the elderly.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors.","authors":"Yingzi Deng, Yifei Li, Ruobing Li, Xiaohui Guo, Yan Liu, Shuqing Wang, Juan Zhang, Mi Li, Lina Zhao, Haifeng Cai, Yunfeng Zhang, Fen Hu","doi":"10.3892/mmr.2025.13625","DOIUrl":"10.3892/mmr.2025.13625","url":null,"abstract":"<p><p>WD repeat and SOCS box containing 2 (WSB2) is an E3 ubiquitin ligase that might be involved in regulating protein stability, thus performing important roles in the development of different types of cancer. However, the biological significance of WSB2 in pan‑cancer is unclear. Pan‑cancer analysis with the online platforms UALCAN and TIMER2.0. revealed that the expression levels of WSB2 were increased in various types of tumors, including breast invasive carcinoma, uterine corpus endometrial carcinoma, liver hepatocellular carcinoma and were decreased in other types such as colon adenocarcinoma, kidney chromophobe and rectum adenocarcinoma, compared with that in their corresponding normal tissues. In addition, pan‑cancer analysis using The Human Protein Atlas database indicated that WSB2 expression levels vary across different cancer types. Reverse transcription‑quantitative PCR (RT‑qPCR) revealed that WSB2 expression varied in 11 different cell lines. Promoter activity analysis indicates that specificity protein 1 carries out a key role in regulating WSB2 expression by binding to its promoter region. UALCAN and Kaplan‑Meier analysis were used to assess the pathological stage and prognostic value of WSB2 in pan‑cancer. Finally, overexpression of WSB2 promoted the proliferation and migration of MCF‑7 and MDA‑MB‑231 cells. Western blotting revealed that WSB2 increased the levels of vimentin, Snail and ERK1/2, and inhibited the expression of p53 and E‑cadherin in MDA‑MB‑231 and MCF‑7 cells. Transcriptome sequencing analysis identified 118 differentially expressed genes associated with WSB2 overexpression, which were mainly enriched in the 'p53 signaling pathway'. Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of mitochondrial Ca²⁺ in stroke: From molecular mechanism to treatment strategy (Review).","authors":"Yanlin Liu, Wenjie Jin, Huixin Zhou, Xiaomei Wang, Hongbin Ren, Xibing Yang, Kaitao Luo, Xiaobing Dou","doi":"10.3892/mmr.2025.13636","DOIUrl":"10.3892/mmr.2025.13636","url":null,"abstract":"<p><p>Mitochondria serve a pivotal role in the pathological mechanisms of stroke, particularly in the regulation of intracellular calcium homeostasis. Stroke‑induced ischemia and reperfusion injury frequently result in disruptions of mitochondrial calcium ion (Ca²⁺) transport, characterized by Ca²⁺ overload. This imbalance directly impairs mitochondrial function and triggers neuronal death. Mitochondrial Ca²⁺ transport involves calcium influx, primarily mediated by the mitochondrial calcium uniporter (MCU) complex, and efflux, primarily through the sodium‑calcium exchanger (NCLX), making this mechanism a critical therapeutic target in stroke. The present review systematically explores the central role of mitochondrial Ca2+ transport in ischemia/reperfusion injury, with an in‑depth analysis of its pathological mechanisms in cellular energy metabolism, oxidative stress and apoptotic signaling pathways. Additionally, this review summarizes recent advancements in therapeutic strategies targeting mitochondrial Ca²⁺ transport, including MCU inhibitors, NCLX activators, antioxidant therapies and combination treatments. It also highlights the potential of Ca²⁺ signaling for early stroke diagnosis and reviews progress in dynamic monitoring technologies for mitochondrial Ca²⁺, such as fluorescence probes and super‑resolution microscopy. Despite significant progress in basic research, challenges remain in translating these findings into clinical applications. Future efforts should focus on elucidating the regulatory mechanisms of mitochondrial Ca²⁺, developing diagnostic tools and optimizing therapeutic interventions to improve stroke prognosis and enhance the quality of life of patients.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between specific microRNA expression and radioresistant conditions in HL60 acute myeloid leukemia cells.","authors":"Hikoto Sugiyama, Megumi Kikuchi, Mitsuru Chiba, Yoichiro Hosokawa, Satoru Monzen","doi":"10.3892/mmr.2025.13645","DOIUrl":"10.3892/mmr.2025.13645","url":null,"abstract":"<p><p>Patients with acute myeloid leukemia (AML) generally receive total body irradiation at a high‑dose rate for the ablation of bone marrow cells, including AML cells. However, in rare cases, radioresistant AML cells appear, interfering with the therapeutic effect. HL60 cells were used to model a radioresistant leukemia cell line that emerged from repeated radiation exposure (Res‑HL60). Notably, the mechanism through which microRNA (miRNA/miR) expression influences radioresistance in this model is unclear. In the current study, the expression profile of the miRNAs included in the small RNAs in Res‑HL60 was analyzed using an miRNA microarray. A total of 1,187 miRNAs were retained for analysis after normalization. Among them, 27 miRNAs (10 upregulated and 17 downregulated in Res‑HL60 cells compared with wild‑type‑HL60 cells) exhibited P<0.05 and fold change >1.5 or <0.66. Furthermore, the expression levels of five miRNAs were validated by reverse transcription‑quantitative PCR: miR‑146a‑5p (upregulated), and miR‑30c‑1‑3p, miR‑671‑5p, miR‑610 and miR‑3675‑5p (downregulated). To investigate the target mRNAs of these five miRNAs, OmicsNet (ver. 2.0) was used. A total of 27 mRNAs were identified as targets of these multiple miRNAs. Furthermore, Reactome analysis revealed enrichment in the following processes 'Cell cycle, Mitotic' (R‑HAS‑69278), 'Apoptosis' (R‑HAS‑109581) and 'Immune system' (R‑HAS‑168256), suggesting that these miRNAs regulate genes involved in these pathways. These findings indicated that the altered expression of five specific microRNAs in radioresistant AML cells may be associated with radioresistant conditions through the modulation of mRNA expression.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Propranolol induces hemangioma endothelial cell apoptosis via a p53‑BAX mediated pathway.","authors":"Tian-Hua Yao, Arekejiang Pataer, Krishna Prasad Regmi, Xi-Wen Gu, Quan-Yan Li, Jing-Ting Du, Su-Meng Ge, Jun-Bo Tu","doi":"10.3892/mmr.2025.13647","DOIUrl":"10.3892/mmr.2025.13647","url":null,"abstract":"<p><p>Following the publication of the above article, the authors have contacted the Editorial Office to explain that Fig. 4A was inadvertently included in this paper, where it had accurately appeared in a paper by the same research group published in 2012 in Journal of <i>Biochemical and Molecular Toxicology</i>. Secondly, the same fluorescence microscopy data had been included in Fig. 6B and C (these data were correctly shown in the figure for panel 6C). The revised versions of Figs. 4 and 6, now featuring the correct data for Figs. 4A and 6B, are shown on the next page. Note that the correction of these data does not grossly affect either the results or conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of <i>Molecular Medicine Reports</i> for allowing them the opportunity to publish this. The authors regret that these errors were included in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 684‑694, 2018; DOI: 10.3892/mmr.2018.9013].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] Inhibition of TLR4 protects rat islets against lipopolysaccharide‑induced dysfunction.","authors":"Xiao Wang, Qin Min Ge, Fan Bian, Yan Dong, Chun Mei Huang","doi":"10.3892/mmr.2025.13622","DOIUrl":"10.3892/mmr.2025.13622","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the lower two flow cytometric plots shown in Fig. 3A on p. 809 (namely, the plots for the 'anti‑TLR4+LPS' and 'TLR4‑shRNA+LPS' experiments), these appeared to show similar groupings of dots, which would not have been anticipated if these experiments had been performed discretely under different experimental conditions, suggesting a fundamental flaw either in the way in which these experiments were performed, or in how the results were outputted. The Editor of <i>Molecular Medicine Reports</i> has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 15: 805‑812, 2017; DOI: 10.3892/mmr.2016.6097].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of AKT1 enhances the capacity of senescent BMSCs to regulate osteoclast activation.","authors":"Chuan Lu, Xingguo Peng, Binbin Zhang, Qi Yan, Bin Dou, Gabriele Karanis, Wenzhuo Gu, Panagiotis Karanis, Kewen Li","doi":"10.3892/mmr.2025.13642","DOIUrl":"10.3892/mmr.2025.13642","url":null,"abstract":"<p><p>Senescent bone mesenchymal stromal cells (BMSCs) play an essential role in bone homeostasis imbalance in osteoporosis; however, the mechanisms through which they regulate osteoclast activation remain unclear. In the present study, highly expressed genes in BMSCs from patients with osteoporosis group were screened using transcriptomic data from the GSE35959 dataset. Subsequently, the <i>AKT1, MAPK3, RELA</i> and colony stimulating factor 1 genes were found to be linked to the PI3K/AKT and MAPK signaling pathways and osteoclast differentiation following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Principal component analysis revealed a distinct clustering of samples by age and disease status. Gene Set Enrichment Analysis further identified significant enrichment of the PI3K/AKT signaling pathway in osteoporosis progression. Considering the notable involvement of the PI3K/AKT signaling pathway in various cellular ageing processes, <i>AKT1</i> was prioritized for further investigation. Analysis of a replicative ageing model of mouse BMSCs showed that AKT1 protein expression was increased in senescent BMSCs and that overexpression of <i>AKT1</i> accelerated the initiation of replicative senescence in this model. Finally, the expression levels of osteoclast differentiation markers (receptor activator of nuclear factor κB, nuclear factor of activated T cells, cytoplasmic 1 and tumor necrosis factor receptor‑associated factor 6) were assessed using tartrate‑resistant acid phosphatase staining. The results from the present study suggested that <i>AKT1</i> plays a role in fostering the replicative senescence of BMSCs and that <i>AKT1</i> activation in senescent BMSCs contributes to osteoclast differentiation. To the best of the authors' knowledge, the present study is the first to demonstrate that AKT1 upregulation in BMSCs with replicative ageing exacerbates senescence and enhances osteoclast differentiation, offering a novel mechanistic insight into senile osteoporosis.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT5 is associated with asthenozoospermia and regulates GC‑2 spd cell proliferation and apoptosis.","authors":"Huilin Xing, Shu Chen, Mingxia Wang, Tingting Zheng, Bo Yang","doi":"10.3892/mmr.2025.13634","DOIUrl":"10.3892/mmr.2025.13634","url":null,"abstract":"<p><p>Infertility is a multifactorial condition that affects ~7% of the male population. The mechanism of male infertility primarily involves intrinsic and environmental factors, of which genetic defects are key for its occurrence. Sirtuin 5 (SIRT5) is primarily localized in mitochondria and associated with male reproduction. SIRT5 is downregulated in asthenozoospermic sperm compared with normal sperm. To explore the role of SIRT5 in male reproduction, Cell Counting Kit‑8, EdU, wound healing, and apoptosis assayswere performed in GC‑2 spd cells (mouse spermatocytes) which revealed that SIRT5 inhibited apoptosis and promoted cell proliferation and migration. Western blotting was performed and the results showed that SIRT5 was involved in the proliferation of GC‑2 spd cells by regulating the PI3K/AKT signaling pathway. The present study demonstrated a mechanism of male infertility, which may aid in its treatment.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"32 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}