Mammalian Genome最新文献

{"title":"Comprehensive bioinformatics analysis and experimental validation reveal the role of circadian rhythm-related genes in the crosstalk between osteoporosis and atherosclerosis.","authors":"Tengyan Liu, Jiashuang Fan, Jianyun Fang, Zhuan Qu, Yaxin He, Kai Yang, Jianlin Yang, Juye Zhang, Dan Yang, Lifen Dai","doi":"10.1007/s00335-026-10216-5","DOIUrl":"10.1007/s00335-026-10216-5","url":null,"abstract":"<p><p>Osteoporosis (OP) and atherosclerosis (AS) are increasingly prevalent in aging populations and frequently coexist, sharing pathological features such as abnormal vascular calcification. However, the common marker genes underlying the crosstalk between OP and AS remain poorly understood. This study aimed to identify shared marker genes and cellular mechanisms contributing to the coexistence of OP and AS. Single-cell RNA sequencing (scRNA-seq) dataset and mRNA expression profiles related to OP and AS were obtained from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses were performed using the R packages Seurat, AUCell, and hdWGCNA to identify circadian rhythm-related genes (CRGs) and associated cell populations. Naturally aged mice and a 0.25% adenine (AD)-induced mouse model were established. Micro-computed tomography (µCT), immunohistochemistry (IHC), immunofluorescence, Von Kossa staining, and RT-qPCR were conducted to experimentally validate the identified common genes. In human bone marrow samples, nine cell lineages comprising 17 subpopulations were identified, while six cell lineages comprising 18 subpopulations were identified in carotid artery samples. Circadian rhythm activity was significantly enriched in bone marrow stromal cells (BMSCs) in OP and vascular smooth muscle cells (VSMCs) in AS. By integrating scRNA-seq and bulk RNA-seq analyses, 69 common genes were identified, of which 15 hub genes were further selected through protein-protein interaction (PPI) network analysis. Experimental validation demonstrated that AEBP1 was markedly upregulated in both naturally aged and AD-induced mice, accompanied by increased PLIN1 expression, reduced osteocalcin (OCN) expression, and enhanced vascular calcification. This study reveals that circadian rhythm-related regulation of BMSCs in OP and VSMCs in AS plays a critical role in their coexistence. Furthermore, we identify shared marker genes, particularly AEBP1, which may serve as potential biomarkers and therapeutic targets for the concurrent development of OP and AS.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.","authors":"Mehwish Anwer, Tetiana Poliakova, Ricardo D'Oliveira Albanus, Mohammad Iqbal H Bhuiyan, Adam M Brickman, Soumilee Chaudhuri, Leah Cuddy, Maxwell Eisenbaum, Kate Foley, Douglas B Gould, Catherine Hall, Costantino Iadecola, Olivia Marola, Christopher M Norris, Alaina Reagan, Julie Schneider, Donna Wilcock, Isabella Xu, Andrew Yang, Gareth Howell, Cheryl L Wellington","doi":"10.1007/s00335-026-10210-x","DOIUrl":"10.1007/s00335-026-10210-x","url":null,"abstract":"<p><p>The first Vascular Contributions to Cognitive Impairment and Dementia (VCID) Workshop, held on May12-16, 2025 at The Jackson Laboratory, provided scientific content and career development training in the latest developments in VCID and Alzheimer's Disease (AD) and related dementia (ADRD). The Workshop aimed to foster interdisciplinary collaborations and empower the next generation of diverse scientists to advance ADRD research from mechanism to intervention. The meeting placed a strong emphasis on neurovascular pathology, its central role in ADRD pathogenesis, its modulation by both central and peripheral factors, and the critical need to dissect the mechanistic basis of VCID through experimental models. The workshop included talks from both faculty and trainees and was bookended by two keynote addresses by Drs. Donna Wilcock and Costantino Iadecola, leaders and pioneers in the VCID field. The second VCID workshop is planned for April 28-May 1, 2026, to be held at Washington University in St. Louis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants.","authors":"U A Rossi, M E Caffaro, D N Gaute, M R Castaño, E Maurizio, M A Poli, C A Rossetti","doi":"10.1007/s00335-026-10212-9","DOIUrl":"10.1007/s00335-026-10212-9","url":null,"abstract":"<p><p>Brucellosis in small ruminants is primarily caused by Brucella ovis and zoonotic B. melitensis. IRF3 is a key transcription factor for IFNα/β gene induction in response to intracellular pathogens. Previously, we identified a genetic association between the rs540 deletion (a-allele) in IRF3 exon 1 and an increased resistance to B. melitensis natural infection in goats. Here, we studied the effect of IRF3 exon 1 polymorphisms on monocyte-derived macrophages (MDMs) in vitro response to Brucella spp. infection, and on the humoral response of goats to Brucella vaccination. Caprine MDMs with the Aa-genotype for rs540 exhibited higher bacterial load (p < 0.01), decreased production of reactive oxygen species (p < 0.05) and lower induction of iNOS, IL-12b, IL-18 and IL-1α mRNA expression (p < 0.05) at 24 h post-infection (h p.i.) with B. melitensis 16 M, in comparison to the aa-genotype. Moreover, the A-allele was associated with an early negativization to Brucella Buffered Plate Antigen test (p < 0.05) and reduced IgG antibody responses (p < 0.05) after Brucella vaccination in goats. On the other hand, ovine MDMs with the T-T-allele for the haplotype rs853-rs301 in IRF3 exon 1 exhibited lower bacterial loads and intracellular bacteria survival rates (ISR) at 24 h p.i. with B. melitensis Rev. 1 and B. ovis PA (p < 0.05), and reduced production of reactive nitrogen species and anion superoxide at 48 h p.i. with B. ovis (p < 0.001). In summary, these results show that polymorphisms in IRF3 exon 1 can influence the immune response of small ruminants to Brucella infection.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated TRF1 mutations alter PARP1 interaction dynamics: an in silico study.","authors":"Apurwa Mishra, Trupti N Patel","doi":"10.1007/s00335-026-10211-w","DOIUrl":"10.1007/s00335-026-10211-w","url":null,"abstract":"<p><p>Telomeric repeat-binding factor 1 (TRF1), a core component of the shelterin complex, is essential for preserving telomere integrity by facilitating efficient replication fork progression across G-rich telomeric DNA. Through its interaction with poly (ADP-ribose) polymerase 1 (PARP1), TRF1 contributes to telomeric chromatin organization and supports the recruitment of helicases required to resolve replication-associated barriers. PARP1 is a central regulator of DNA repair and fork protection, navigating chromatin through a dynamic “monkey-bar” transfer mechanism in which its domains alternately engage distinct DNA sites. Pharmacological inhibition disrupts this dynamic behavior and induces PARP trapping, a cytotoxic state exploited therapeutically in DNA repair-deficient cancers. To explore whether TRF1 mutations could modulate PARP1 interaction dynamics in a manner conceptually analogous to trapping, we employed an integrative in silico pipeline combining pathogenicity prediction, structural modeling, protein-protein docking, and molecular dynamics simulations. Among mutations reported in COSMIC and dbSNP, four variants (D422G, W424L, R425G, and M427K) emerged as candidates with high disruptive potential, with the Myb-domain variant W424L prioritized for detailed analysis. Structural and dynamic analyses revealed that the W424L substitution alters local TRF1–PARP1 contact networks and biases PARP1 toward a more conformationally constrained interaction state, without altering the primary interface geometry. Collectively, these findings support a model in which specific TRF1 mutations may reprogram PARP1 interaction dynamics at telomeres. While experimental validation will be required, this work provides a hypothesis-generating framework suggesting that TRF1 variant profiling may help identify tumors with altered PARP1 dependency and differential sensitivity to PARP-targeted therapies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The North African maternal genetic diversity enriched by historical migrations: insights from a comprehensive analysis of complete mitogenomes.","authors":"Nasma Boumajdi, Houda Bendani, Lahcen Belyamani, Azeddine Ibrahimi","doi":"10.1007/s00335-026-10209-4","DOIUrl":"10.1007/s00335-026-10209-4","url":null,"abstract":"<p><p>North Africa has experienced significant gene flow throughout history, with Morocco occupying a strategic location at the crossroads of Africa and Europe. In this study, we compiled 869 complete mitogenome sequences from six North African populations to explore genetic diversity, haplogroup distributions, and phylogenetic relationships, with a specific emphasis on the Moroccan population. We obtained a high haplotype diversity across all populations, and neutrality tests yielded significant negative values, consistent with demographic expansion. We identified 56 haplogroups, dominated by U6, H, and L. Genetic differentiation between populations was low (FST = 0.001-0.014), and analysis of molecular variance indicated that most genetic variation occurs within populations, and reinforces the presence of a genetically cohesive Maghreb core. Phylogenetic and NeighborNet analyses showed that Moroccan sequences are widely distributed across haplogroups, with deep branching of macro-haplogroup L subclades, indicating early human migration patterns, including out-of-Africa dispersal and subsequent back-migrations. Bayesian demographic analysis of the prevalent haplogroups in Morocco revealed distinct evolutionary trajectories: an expansion of haplogroup L, a decline of U6, and an expansion of H. To complement the maternal perspective, we analyzed published Y-chromosome STR data from 2114 North African males. Haplotypic diversity remains high (> 0.97), and the haplogroup E-M81 predominates in Moroccan, Algerian, and Tunisian populations. Low pairwise Rst values further confirm the genetic homogeneity of North Africa and reinforce the strong cohesion of the Maghreb core. This study highlights a rich genetic heritage shaped by ancient and ongoing gene flow in North Africa.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of SOX4 attenuates sepsis myocardial injury by inhibiting the EZH2/H3K27me3/SOCS3 axis.","authors":"Hongyan Zhao, Weirong Tao, Rong Huang, Jing Cao, Chao Xu","doi":"10.1007/s00335-026-10206-7","DOIUrl":"10.1007/s00335-026-10206-7","url":null,"abstract":"<p><p>Inhibition of SOX4 has been reported to ameliorate myocardial ischemic injury, yet its role in sepsis myocardial injury remains unknown. To explore the protective effects and mechanisms of SOX4 inhibition in septic myocardial injury. AC16 cardiomyocytes were exposed to LPS to mimic sepsis-induced myocardial injury. Cell viability was measured by CCK-8 assay, apoptosis by flow cytometry and TUNEL staining, and apoptosis-related proteins by western blot. The connection between SOX4 and EZH2 was validated using co-immunoprecipitation (co-IP) assay and immunofluorescence. Additionally, chromatin immunoprecipitation (ChIP) was employed to detect the enrichment of H3K27me3 in SOCS3 promoter region. The results showed that SOX4 and EZH2 were significantly elevated in septic patients, and their expression levels were positively correlated. In LPS-treated AC16 cardiomyocytes, the expressions of SOX4 and EZH2 increased, while the expression of SOCS3 decreased. Knockdown of SOX4 enhanced AC16 cell viability and inhibited LPS-induced apoptosis. SOX4 and EZH2 colocalized within AC16 cells, and co-IP assays confirmed their interaction. Elevated EZH2 expression reduced the protective impact of SOX4 knockdown in AC16 cells. Silencing EZH2 reduced the enrichment of H3K27me3 in SOCS3 promoter region and thereby promoting SOCS3 expression. Overexpression of SOCS3 promoted AC16 cell survival and partially reversed the damaging effect of EZH2 overexpression on cell survival. Animal experiments confirmed that knockdown of SOX4 attenuated myocardial injury in CLP sepsis mouse model. Knockdown of SOX4 reduces the H3K27me3 methylation level of the SOCS3 promoter by inhibiting EZH2 expression, thereby promoting SOCS3 expression and attenuating myocardial injury.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of humeral fracture healing by miR-21 through SMAD7-mediated activation of Wnt/β-catenin signaling.","authors":"Juan Liu, Hong Ren, Shuo Zhang, Guiyong Yu","doi":"10.1007/s00335-026-10208-5","DOIUrl":"10.1007/s00335-026-10208-5","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are key regulators of bone regeneration. We investigated the role of miR-21 in humeral fracture (HF) healing, focusing on its interaction with the SMAD7/Wnt/β-catenin signaling axis. Serum and tissue levels of miR-21 were analyzed in HF patients and healthy controls using qRT-PCR. A rat HF model was established, and agomiR-21 was administered to evaluate its effect on fracture healing. Histological analysis using hematoxylin and eosin (H&E) staining was performed to assess bone tissue morphology and fracture healing. In vitro, MC3T3-E1 osteoblasts were transfected with miR-21 mimics to assess cell viability (CCK-8), proliferation (EdU), apoptosis (flow cytometry), migration (Transwell assay), and osteogenic differentiation (Western blot). The downstream target of miR-21 was identified using bioinformatics and validated via luciferase reporter and RNA immunoprecipitation assays. Rescue experiments involving SMAD7 overexpression and Wnt/β-catenin inhibitors (DKK1) were conducted to explore the mechanism of action. Serum analysis revealed reduced β-catenin and phosphorylated GSK3β (p-GSK3β) levels in humeral fracture (HF) patients compared to healthy controls, indicating suppressed Wnt/β-catenin signaling. In MC3T3-E1 cells, miR-21 overexpression enhanced osteogenic markers and increased total β-catenin, active β-catenin, and p-GSK3β levels, confirming activation of the Wnt/β-catenin pathway. Dual-luciferase and expression analyses demonstrated that miR-21 directly targets SMAD7, a known Wnt pathway inhibitor. Co-transfection with SMAD7 reversed the effects of miR-21 on β-catenin activation, ALP activity, and osteogenic gene expression. Additionally, miR-21 knockdown impaired osteogenesis, further supporting its regulatory role. Importantly, in vivo, agomiR-21 treatment enhanced osteoblast activity and significantly promoted bone healing in a rat fracture model, reinforcing the therapeutic potential of miR-21-mediated SMAD7 suppression and Wnt/β-catenin pathway activation in bone regeneration. miR-21 promotes bone regeneration after humeral fracture by enhancing osteoblast function and activating Wnt/β-catenin signaling through direct inhibition of SMAD7.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome assembly of the Neotropical marsh rat Holochilus nanus (Cricetidae: Sigmodontinae) brings insights on B and sex chromosome evolution.","authors":"Camila Nascimento Moreira, Jordana Oliveira, Yatiyo Yonenaga-Yassuda, Valter Aragão do Nascimento, Ivan Rodrigo Wolf, Cesar Martins","doi":"10.1007/s00335-026-10205-8","DOIUrl":"10.1007/s00335-026-10205-8","url":null,"abstract":"<p><p>The Neotropical region comprises approximately 27% of mammal diversity, and rodents of the tribe Oryzomyini represent a significant portion of that. This diversity is reflected in the karyotype variability of the tribe, with a huge number of chromosomal rearrangements involving autosomal, sex, and B chromosomes. Supernumerary B chromosomes were described for more than 10 species, four of them belonging to the genus Holochilus. Therefore, we sequenced the genome of two H. nanus specimens with different karyotypes: a female with (HNA-XXB) and a male without (HNA-XY) a B chromosome. We also sequenced previously flow-sorted chromosomes from this species: two B (HNA-B1, HNA-B2) and the Y chromosome (HNA-Y). Genome assemblies of HNA-XY and HNA-XXB were compared, enabling the identification of ancient genome duplications that could result from fragments of the B chromosome. In addition, more than fifty scaffolds containing sequence blocks shared between the libraries of HNA-B1, HNA-B2, and HNA-Y were found. The sequence blocks mapped in metaphases of H. nanus presented hybridization signals on the centromeric region of the chromosomes, highlighting that the centromeric composition of H. nanus is highly variable. In addition, qPCR and RT-qPCR analysis evidenced that these sequences are expressed, indicating a role in the genome structure. Briefly, supernumeraries of H. nanus appear to be a mosaic of the genome and may contain genes and sequences crucial for its maintenance, in addition to its repetitive DNA fraction.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics and machine learning prioritize key immune genes for multiple sclerosis risk prediction.","authors":"Ming Chen, Duran Zhao, Haiping Fan, Xiaojun Zeng, Wei Zhang, Lijuan Li, Wei Li","doi":"10.1007/s00335-026-10207-6","DOIUrl":"10.1007/s00335-026-10207-6","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a complex autoimmune disease with strong genetic components, but its genetic mechanisms remain largely underexplored. We aimed to pinpoint causal genes and evaluate their utility for MS risk prediction. We integrated MS genome-wide association study summaries with brain-derived splicing quantitative trait loci (sQTLs) and expression quantitative trait loci (eQTLs) via summary-data-based Mendelian randomization (SMR) and colocalization analyses to identify potential causal genes. Weighted gene coexpression network analysis (WGCNA) of the E-MTAB-5151 dataset identified MS-associated gene modules. LASSO regression determined the core gene signature. GO and KEGG enrichment analyses, immune infiltration, and gene set enrichment analysis (GSEA) explored the biological relevance. Using an independent protein quantitative trait loci (pQTL) dataset, key genes were further validated for pQTL-MS associations. SMR identified 28 sQTL genes and 66 eQTL genes for MS, 23 and 51 of which passed the colocalization tests, respectively. WGCNA identified three MS-associated modules, and their intersection with SMR genes prioritized 23 key genes. Functional enrichment analysis of the module genes and SMR genes highlighted the consistent involvement of immune-related pathways in MS, including lymphocyte activation and NF-κB signalling. LASSO regression established a 10–gene signature (ACP2, IL7, MYNN, RGS1, SAE1, SP140, TRAF3, TSPAN31, TYMP, and ZC2HC1A) with high predictive accuracy (AUC = 0.983 in internal validation; AUC > 0.70 across three external datasets). Immune infiltration analysis revealed a consistent immune cell expression pattern, in which the expression of MS risk genes was positively associated with naive CD4+ T cells and resting mast cells, but negatively associated with activated mast cells. In contrast, MS protective genes exhibited the opposite pattern. Furthermore, the integration of the MS genome-wide association study statistics validated ZC2HC1A and TRAF3 at the protein level. GSEA further linked both genes to the Hedgehog signalling pathway. Integrating genomic, transcriptomic, and proteomic data, we identified candidate causal genes for MS with robust evidence. ZC2HC1A and TRAF3 have emerged as promising biomarkers and mechanistic candidates for MS. Future follow-up functional studies are warranted to elucidate their molecular roles in MS pathogenesis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAPTM5 potentiates airway remodeling by regulating MAPKs-mediated airway smooth muscle cells' dysfunction.","authors":"Lijiao Jiang, Yaping Ying, Haihong Jin, Tingmin Zhou","doi":"10.1007/s00335-026-10204-9","DOIUrl":"10.1007/s00335-026-10204-9","url":null,"abstract":"<p><p>Airway remodeling is one of the hallmarks of asthma in which the dysregulation of airway smooth muscle cells (ASMCs) plays a part. However, the role of LAPTM5 in asthma is largely yet to be elucidated. In this study, the expression of LAPTM5 in ASMCs from the asthmatics and non-asthmatics was inspected using a publicly available dataset. The expression of LAPTM5 was next examined in ASMCs challenged by platelet-derived growth factor (PDGF). The establishment of LAPTM5 knockdown ASMCs was conducted with small interference RNA, and the proliferation, migration, and extracellular matrix production of ASMCs in the presence of PDGF were further determined. The activation of MAPK signaling was detected with western blot in LAPTM5 knockdown or overexpression ASMCs. Two MAPKs inhibitors, SB203580 and U0126, were employed to investigate the effects of MAPKs blockade on the proliferation, migration, and extracellular matrix production on LAPTM5-overexpressed ASMCs. The results revealed that the overexpression of LAPTM5 in the ASMCs of the asthmatics, and the knockdown of LAPTM5 in ASMCs suppressed PDGF-induced proliferation, migration, and extracellular matrix production. Furthermore, phosphor-p38 and -ERK enhanced by PDGF were reduced by LAPTM5 ablation. Pharmacal inhibition of MAPKs effectively abrogated the dysregulation of ASMCs induced by LAPTM5 overexpression in the presence of PDGF. Collectively, the expression of LAPTM5 is closely associated with the dysregulation of ASMCs and the consequent airway remodeling, and we proposed that LAPTM5 is a potential therapeutic target in asthma.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":"36"},"PeriodicalIF":2.6,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}