Ask about this productRelated genes to: TGM4 antibody
- Gene:
- TGM4 NIH gene
- Name:
- transglutaminase 4
- Previous symbol:
- -
- Synonyms:
- TGP
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1995-02-07
- Date modifiied:
- 2016-10-05
Related products to: TGM4 antibody
Related articles to: TGM4 antibody
- The early detection of prostate and testicular tumors remains challenging as standard diagnostic tools often lack sensitivity and produce ambiguous results. Seminal fluid is a biologically rich medium that closely reflects the state of male reproductive tissues and has therefore emerged as a promising source of non-invasive molecular biomarkers. This study aimed to critically evaluate the evidence regarding cell-free DNA, RNA, proteins and metabolites in seminal fluid, and to assess their potential for improving the early detection of male reproductive cancers. A systematic review was performed according to PRISMA guidelines. Comprehensive searches of the PubMed and Scopus databases were conducted to identify original clinical studies analyzing molecular biomarkers in seminal fluid from patients with prostate or testicular tumors. For each study, data were extracted on biomarker types, cohort characteristics, analytical methods and diagnostic performance. Forty-two eligible studies were included, covering multiple biomarker classes. Most were observational, single-center investigations classified as level 3b evidence. Across the different types of biomarkers, seminal fluid was associated with tumor-associated molecular changes. Alterations in the concentration, fragmentation and methylation patterns of cell-free DNA (e.g., GSTP1, RARβ2, LGALS3 and OCT3/4) distinguished malignant from benign conditions with sensitivities of up to 80-100%. RNA-based markers, including microRNAs, small non-coding RNAs, and tRNA fragments, showed improved performance in several studies, with multimarker models achieving areas under the curve (AUCs) of 0.85-0.93. Proteomic analyses identified high-specificity candidates such as TGM4, AMACR, PROS1 and DKK3. Metabolomic profiling further strengthened the diagnostic potential; reduced seminal citrate outperformed prostate-specific antigen (AUC 0.748 vs. 0.548), and reproducible shifts in amino acid and lipid profiles were observed in testicular tumors. However, substantial heterogeneity in study design, patient selection, and analytical platforms was observed. Risk of bias varied, and large prospective validation cohorts were lacking. Current evidence suggests that seminal fluid contains molecular signals associated with tumors that could be used for diagnosis. However, the available data are predominantly exploratory and methodologically heterogeneous. Before seminal fluid-based biomarkers can be considered for routine clinical implementation, robust prospective studies with standardized protocols are required. - Source: PubMed
Publication date: 2026/04/23
Sagitova Guzel RSlizova Anna VMorozov Andrey OFatyanova Anastasia SWarkiani Majid EbrahimiZvyagin Andrei VRzhevskiy Alexey S - The transforming growth factor-β (TGF-β) mimics TGM1 and TGM4 are modular proteins expressed by the parasite Heligmosomoides polygyrus. Each comprises 5 complement control protein (CCP) domains binding the TGF-β receptors TGFBR1 (Domains 1 and 2) and TGFBR2 (Domain 3), whereas Domains 4 and 5 bind cell surface co-receptors including CD44. Despite sharing 86% amino acid identity, TGM1 and TGM4 differ functionally in key respects of affinity for mammalian TGFBRs and interactions with cell surface co-receptors. Although both induce T cell expression of the transcription factor Foxp3, TGM1 activates intracellular SMAD signaling in fibroblasts, whereas conversely, TGM4 blocks SMAD responses to TGF-β or TGM1 in fibroblasts. By recombining and/or deleting domains, we identified that the TGFBR1-binding Domains 1 and 2 of TGM4 confer antagonist activity, which is dependent on the CD44 co-receptor interacting domains (Domains 4 and 5); antagonism is enhanced but not fully dependent on binding to TGFBR2. TGMs lack interchain disulfide bonds, in distinction to TGF-β, which is a covalently linked dimeric cytokine. Dimerization of TGM4 as an Fc fusion protein converted it from an inhibitor to an activator of SMAD signaling in fibroblasts and enhanced Foxp3 induction, indicating that high avidity interactions (either monomer/dimer on T cells or only dimer on fibroblasts) drive TGF-β signaling. However, when TGM4 is below an avidity threshold, it binds receptors in an antagonistic mode. These results advance our understanding of the mechanism of action of these parasite-encoded products and uncover new tools modulating TGF-β functions in health and disease. - Source: PubMed
Cunningham Kyle TCiancia ClaireCampion Tiffanyvan Dinther MaartenDavis NadiaDuffy AnjaHeawood Anna L LPower LukeSanders AnnaSingh Shashi PSmyth Danielle JThompson ElizabethWhite RubyHinck Andrew PTen Dijke PeterMaizels Rick M - This study aimed to evaluate tissue-associated circulating cell-free DNA (cfDNA) as indicators of radiotherapy-related effects and treatment-associated toxicity in prostate cancer. In addition, inter-individual variability in these markers and their responses to radiotherapy-induced cystitis and rectitis were investigated. The DNA methylation status of six tissue-associated genes representing the prostate (KLK3, TGM4), colon (MUC2, MS4A12), and bladder (UPK2, DHRS2) was analyzed in serum-derived cfDNA using methylation-sensitive melting curve analysis (MS-MCA). Five of the six analyzed genes demonstrated significantly higher relative DNA levels in patients with prostate cancer compared with controls. Radiotherapy did not significantly alter the relative DNA levels of these tissue-associated genes. However, cfDNA fragmentation was significantly increased in the post-treatment group compared to the pre-treatment group. Notably, 79-bp DNA fragments were significantly more abundant than 230-bp fragments. In the post-treatment group, no significant correlations were observed between cfDNA fragmentation and the relative DNA levels of most targets, except for an association between the 230-bp fragment and TGM4 relative DNA levels. These findings suggest limited coupling between cfDNA fragmentation patterns and tissue-associated cfDNA release. Marked inter-individual variability in cfDNA methylation signatures was observed across all examined CpG-containing regions except UPK2. This variability did not change significantly following radiotherapy and may therefore limit the utility of these assay regions for monitoring individual radiation-induced tissue damage. Furthermore, no significant changes in methylation profiles of colon- or bladder-associated genes were detected in patients who developed radiotherapy-induced rectitis or cystitis. Overall, increased cfDNA fragmentation following radiotherapy and substantial inter-individual variability in methylation profiles across tissue-associated regions may mask tissue-associated cfDNA signals, thereby complicating the assessment of radiation-induced tissue damage. - Source: PubMed
Publication date: 2026/03/06
Bahtiyar NurtenMermut OzlemFirtina SinemOzaydin AhmetSuleymanova AishaIsikgil BegumOnaran İlhan - Accumulating evidence has indicated that microRNAs (miRNAs) participate in chicken skeletal muscle development by post-transcriptionally regulating myogenesis-related gene expression. Our previous study showed that miR-34c-5p inhibited proliferation and myogenic differentiation of chicken primary myoblasts (CPMs), but its molecular mechanisms remain unclear. Here, miR-34c-5p was overexpressed in CPMs for transcriptome sequencing. The 159 differentially expressed genes (DEGs) were identified and were mainly involved in myogenesis-related processes and signaling pathways, including cytoskeleton regulation, PPAR, and cardiac muscle contraction. Intersection of DEGs and predicted targets of miR-34c-5p yielded 15 candidate genes. Of these, miR-34c-5p could inhibit the mRNA expression of MYH7B and TGM4 genes by directly interact with their 3' untranslated regions as determined by dual-luciferase reporter systems Gain- and loss-of-function assays demonstrated that TGM4 gene could promote CPMs proliferation. These findings elucidate the regulatory network of miR-34c-5p underlying myogenesis and provide potential molecular marker for genetic improvement of meat production in chicken. - Source: PubMed
Publication date: 2026/02/20
Li ShuohanZhang KeTian YixiangGuo MiaomiaoWang XuDing PengGuo YulongLi HongLi ZhuanjianTian YadongKang XiangtaoLiu XiaojunTian Weihua - Cell-free seminal mRNA (cfs-mRNA) has been utilized in the diagnosis of diseases affecting the male reproductive system. However, the existing detection methods are time-consuming and labor-intensive. Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method with high efficiency and accuracy; however, it has not been applied to cell-free RNA in human body fluids. Herein, we designed gene-specific primers for TGM4 and DDX4 and established a reverse transcription-LAMP (RT-LAMP) system for detecting their cfs-mRNA. The sensitivity of this system was investigated using RNA standards. The optimal conditions were 65 ℃ for 30 to 45 min for TGM4 and 65 ℃ for 45 to 60 min for DDX4. When incubated at 65 ℃ for 45 min, the limit of detection (LOD) for DDX4 mRNA was 124 copies, which increased to 37 copies when the reaction time was extended to 90 min. We also validated the RT-LAMP reaction using semen plasma samples from 20 azoospermic patients and identified 3 DDX4 cfs-mRNA negative patients among 72 azoospermic patients in total. In conclusion, this study establishes a novel RT-LAMP method for rapid and sensitive detection of TGM4 and DDX4 cfs-mRNA in seminal plasma. RT-LAMP is a rapid, sensitive and specific method for cfs-mRNA detection, which has the potential to be used in the diagnosis of male reproductive system diseases, RNA detection in other body fluids, and commercial promotion. The validated technique offers significant potential for efficient diagnosis of male reproductive disorders and broader RNA detection applications. - Source: PubMed
Publication date: 2025/10/13
Zhao JieyiZhang XiaokeLiu XinyuTan XiaLuo JingwenZhu ShiqingKang YafeiWang XinyiLi Honggang