Ask about this productRelated genes to: MAPKAPK3 protein
- Gene:
- MAPKAPK3 NIH gene
- Name:
- MAPK activated protein kinase 3
- Previous symbol:
- -
- Synonyms:
- 3pK, MAPKAP3, 3PK
- Chromosome:
- 3p21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-03-26
- Date modifiied:
- 2019-04-12
Related products to: MAPKAPK3 protein
Related articles to: MAPKAPK3 protein
- Increasing evidence indicates that cellular senescence, metabolic dysfunction, stromal remodeling, and immune perturbation collectively contribute to disease progression. However, senescence-related biomarkers with diagnostic potential and microenvironmental relevance in sarcopenia remain insufficiently defined. We integrated bulk transcriptome data from sarcopenia and control samples, with senescence-associated gene sets from the GenAge and CellAge databases to identify senescence-related differentially expressed genes (DEGs). Transcriptomic landscape was characterized via principal component analysis (PCA), volcano plot visualization, heatmap clustering, functional enrichment analysis, and gene set enrichment analysis (GSEA). Candidate diagnostic genes were screened using three complementary machine learning algorithms: least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF). Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis, nomogram construction, and decision curve analysis (DCA). Immune and stromal infiltration patterns were estimated via single-sample gene set enrichment analysis (ssGSEA) and xCell deconvolution. Single-cell RNA sequencing (scRNA-seq), pseudotime trajectory analysis, hub gene-centered GSEA/GSVA, weighted gene co-expression network analysis (WGCNA), immune checkpoint correlation analysis, and ligand-receptor communication analysis were further performed to investigate the cellular localization, dynamic expression patterns, and potential regulatory roles of hub genes. Animal experiment was conducted to validate the reliability of the main analyses. A total of 42 senescence-related DEGs were identified in sarcopenia. Functional enrichment analyses indicated significant involvement of kinase activity regulation, receptor tyrosine kinase-related signaling, JAK-STAT signaling, AMPK signaling, ERK1/2 cascade regulation, and extracellular matrix-related pathways. GSEA revealed positive enrichment of NABA Core Matrisome and negative enrichment of the citric acid cycle and respiratory electron transport pathway in sarcopenia. Integrative machine learning analysis converged on PCK1, EGFR, and MAPKAPK3 as senescence-related hub genes. PCK1 and EGFR were significantly upregulated in sarcopenia, whereas MAPKAPK3 was significantly downregulated. The individual AUC values for diagnosis were 0.777 (PCK1), 0.764 (EGFR), and 0.751 (MAPKAPK3), while the combined three-gene model achieved an improved AUC of 0.801. Immune infiltration analysis showed that PCK1 and EGFR were positively associated with fibroblast-related stromal signatures, while MAPKAPK3 showed an opposite trend and was more closely linked to Th1-cell-related immune features. Single-cell and pseudotime analyses further demonstrated that these hub genes exhibited distinct cellular localization and dynamic expression patterns across the myogenic lineage. WGCNA and immune checkpoint analyses supported their participation in broader regulatory networks associated with sarcopenia. In addition, EGFR-centered virtual knockout analysis revealed significantly altered intercellular communication, especially involving fibroblast- and muscle-related compartments. Experimental validation in a rat sarcopenia model confirmed the bioinformatics findings: PCK1 and EGFR mRNA and protein levels were significantly upregulated, while MAPKAPK3 was significantly downregulated in the sarcopenia group compared with controls (all P < 0.05), supporting the reliability of the identified hub genes. PCK1, EGFR, and MAPKAPK3 are senescence-related candidate biomarkers in sarcopenia and may reflect distinct yet interconnected biological processes involving metabolic adaptation, stromal remodeling, immune microenvironment alteration, and myogenic dysregulation. Among them, EGFR may represent an important signaling node associated with skeletal muscle microenvironmental communication in sarcopenia. - Source: PubMed
Publication date: 2026/08/26
Chen YanMa KewenHuang TianchongGao JingFeng Xiaodong - Microplastic (MP) pollution has become a global aquatic environmental issue, yet its long-term toxic effects on aquatic organisms remain poorly understood. In this study, grass carps (Ctenopharyngodon idella) were subjected to thirty-week dietary exposure to polystyrene microplastics (PS-MPs) to systematically evaluate the effects on histology, immune signaling, and intestinal microbiota. Histopathological examination revealed that PS-MPs exposure induced focal necrosis, increased melanomacrophage centers, and sinusoidal congestion in the spleen, while the intestine exhibited villus fusion, disordered arrangement, epithelial edema, and lymphocyte infiltration. Transcriptomic analysis further identified 2975 differentially expressed genes (DEGs) in the spleen. Functional enrichment analysis revealed that these DEGs were significantly associated with cytokine-cytokine receptor interaction, Toll-like receptor, RIG-I-like receptor, and NOD-like receptor signaling pathways. Notably, the MAPK-associated gene mapkapk3 was significantly upregulated, whereas the immune-regulatory receptor gene IL20RA was downregulated, suggesting disruption of immune homeostasis and remodeling of innate immune signaling. Gut microbiota analysis revealed marked dysbiosis characterized by increased relative abundances of Fusobacteriota (57%) and Proteobacteria (35%), accompanied by pronounced reductions in Bacteroidota and Firmicutes. All alpha diversity indices (Chao1, Ace, Shannon, Simpson) were significantly decreased, and beta diversity analyses (PCA, PCoA, NMDS) demonstrated clear separation between groups. The opportunistic pathogen Aeromonas veronii was significantly enriched and identified as a key biomarker in the PS-MPs group. Collectively, long-term PS-MPs exposure induced structural tissue damage, altered immune-related transcriptional profiles involving mapkapk3 and IL20RA, and promoted gut microbial dysbiosis with enrichment of opportunistic pathogens, thereby potentially increasing host susceptibility to environmental stressors. These findings provide mechanistic insight into the ecological health risks posed by chronic MP exposure in freshwater fish. - Source: PubMed
Publication date: 2026/07/13
Chen YixuanZheng MingpengXie MinminZhang PinpinZhang YingLiu YiZhou Chuang - Chaperone-mediated autophagy (CMA) plays an important role in tumor progression and remodeling of the tumor immune microenvironment. However, its functional heterogeneity, immune associations, and clinical significance in colon cancer remain unclear. - Source: PubMed
Publication date: 2026/06/03
Zhang JiaxingZhao XiaodanWang Yong - Sarcopenia and chronic pain are prevalent age-related conditions with substantial health impacts, yet their causal relationship remains unclear. Our aim is to study the bidirectional causal relationship among these diseases and identify potential therapeutic targets through genetic methods, as well as explore new therapeutic drugs. We performed bidirectional Mendelian randomization and Bayesian colocalization analyses using GWAS data from sarcopenia and chronic pain studies to explore their genetic relationships. Through integrating PheWAS and DrugBank analyses, we identified potential therapeutic candidates. We then evaluated these candidates using FAERS database for safety profiles and explored their pathway-level associations through drug-omics data. Our analyses revealed significant bidirectional genetic associations between sarcopenia and chronic pain, identifying 9 shared genes (MAPKAPK3, MYBPC3, POLR2L, DDAH1, FAM177B, ABCC8, RMDN3, RFTN2, and SUOX). Four genes (MAPKAPK3, DDAH1, ABCC8, and SUOX) were identified as druggable targets, with 18 compounds (including approved, investigational, and preclinical drugs) identified as potential therapeutic candidates. After FAERS screened and excluded candidate drugs that might aggravate muscle or pain symptoms, dexlansoprazole and glipizide showed relatively favorable safety profiles among compounds targeting these genes. Subsequent drug-omics analysis identified pathway enrichments consistent with muscle and pain-related processes, though clinical efficacy remains unestablished. This study provides genetic evidence for a causal bidirectional relationship between sarcopenia and chronic pain, identifying potential therapeutic targets. However, findings are based on computational analyses of summary-level data without experimental validation. The identified drug candidates warrant further rigorous experimental and clinical investigation for repurposing strategies in managing these conditions. - Source: PubMed
Li JuanHuang JiaqiHan Jiang - Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with incompletely elucidated underlying biological mechanisms. Circulating proteins serve as an intermediate molecular layer linking genetic variation to downstream biological processes. This study aimed to systematically investigate the causal associations between the plasma proteome and ASD risk, followed by multi-omic and clinical validation. - Source: PubMed
Publication date: 2026/04/24
Wang LihongLiu TianciYu LianhuLiu ZhiyueChe ChaoYu XiaoxiaoCai ZhifengCao Aihua