Ask about this productRelated genes to: LRG1 protein
- Gene:
- LRG1 NIH gene
- Name:
- leucine rich alpha-2-glycoprotein 1
- Previous symbol:
- -
- Synonyms:
- LRG
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-12
- Date modifiied:
- 2016-06-06
Related products to: LRG1 protein
Related articles to: LRG1 protein
- Pancreatic cancer (PC) is a malignant tumor that often presents no obvious symptoms in its early stages, leading to late diagnosis and poor prognosis. Therefore, developing molecular markers for PC is essential for improving early diagnosis, optimizing treatment strategies, and enhancing patient outcomes. In this study, PC tissue and matched adjacent non-cancerous tissue were collected from patients. For in vitro analysis, the PC cell lines BxPC-3 and SW1990 were used. M2 macrophages were induced in THP-1 cells. Gene expression at both mRNA and protein levels was measured using real-time quantitative PCR and Western blotting. Cell counting kit-8 assay was used to evaluate cell activity. Flow cytometry was used to assess the cell apoptosis rate and M2 macrophage biomarkers. Transwell and wound-healing assays were used to determine cell migration and invasiveness. Co-immunoprecipitation assay was used to evaluate the binding relationship between leucine-rich α-2 glycoprotein 1 (LRG1), chemokine receptor 1 (CCR1), and GALNT6. LRG1 expression was upregulated in PC tissues compared to that in normal tissues. Co-culture with M2 macrophages enhanced gemcitabine (GEM) resistance, cell migration, and PC cell invasion. LRG1 overexpression in PC cells enhanced the effect of M2 macrophage cells to exacerbate GEM resistance, cell migration, and invasion, while LRG1 knockdown exhibited an opposite effect. LRG1 interacted with CCR1 to enhance PI3K/AKT signaling, thereby affecting GEM resistance, migration, and PC cell invasion. Moreover, GALNT6 was confirmed as an upstream regulator of LRG1, which glycosylated LRG1 and increased its stability. Rescue experiments demonstrated that GALNT6 promoted GEM resistance, movement, and invasion abilities of PC cells by regulating LRG1. The role of LRG1 in the interaction between PC cells and M2 macrophages was also verified in the xenograft model. These findings demonstrate that GALNT6-glycosylated LRG1 mediates the interaction between M2 macrophages and PC cells by activating CCR1. This study may provide promising therapeutic targets for PC treatment. - Source: PubMed
Publication date: 2026/08/08
Hong DengjianSu HangSu YexiongCai Duxiong - Alcohol-related liver disease (ALD) is a major cause of liver-related morbidity and mortality worldwide, yet the associations linking alcohol-induced gut microbial alterations to metabolic remodeling and hepatocyte dysfunction remain incompletely understood. Here, we applied an integrative multi-omics strategy combining untargeted fecal metabolomics, shotgun metagenomics, mouse liver bulk RNA sequencing, and reanalysis of publicly available human hepatic single-cell and bulk transcriptomic datasets to characterize alcohol exposure-associated gut-liver immunometabolic features. In a mouse model of acute ethanol-induced liver injury, fecal metabolomic and metagenomic profiling revealed marked alterations in microbial functional potential and fecal metabolic composition, identifying six convergent metabolic pathways across fecal multi-omics layers, including nucleotide metabolism, the pentose phosphate pathway, histidine metabolism, glycerophospholipid metabolism, glycine/serine/threonine metabolism, and the phosphotransferase system. Reanalysis of human ALD single-cell transcriptomes showed hepatocyte-enriched activity patterns for several corresponding pathways, suggesting potential pathway-level associations between fecal metabolic alterations and hepatic transcriptional responses. Integrative transcriptomic analysis further identified a ten-gene hepatocyte-associated signature, comprising LRG1, ORM1, ORM2, TAT, HP, FGB, FGG, ITIH3, NNMT, and AGT, which was associated with pathway activity and showed consistent upregulation across acute ethanol-induced liver injury and human ALD/AH transcriptomic datasets. In an external human cohort, this signature stratified patients into exploratory molecular subgroups with distinct metabolic pathway activities and clinical outcome distributions. Collectively, these findings provide a hypothesis-generating multi-omics framework for investigating alcohol-related liver injury and support further validation in chronic ethanol exposure models and functional studies. - Source: PubMed
Publication date: 2026/07/22
Ding RanQi FanDai QianqianLi KangfanZhang Yuan - Previous studies show that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) enhances brain repair and functional recovery during the chronic phase of severe traumatic brain injury (TBI), but the underlying mechanisms remain unclear. Here, we investigated whether SCF + G-CSF modulates brain immune cell states during chronic TBI. In a controlled cortical impact mouse model, SCF + G-CSF was administered subcutaneously for 5 consecutive days beginning 8 months post-injury. CD11b⁺ brain immune cells, including microglia and monocytes/macrophages (Mo/Mac), were isolated one day after the final injection and analyzed by single-cell RNA sequencing. Integrated analyses revealed more extensive transcriptomic changes in Mo/Mac than in microglia following SCF + G-CSF treatment. Flow cytometry confirmed a significant increase in the CD11b/CD45 Mo/Mac population following treatment. In microglia, SCF + G-CSF modestly upregulated genes such as S100a8, S100a9, Mir682, and Rpl37rt. In contrast, Mo/Mac showed robust upregulation of genes including Wfdc17, Ifitm1/2/3, Tspo, Lrg1, and Igfbp6, consistent with transcriptomic signatures associated with antiviral defense, anti-inflammatory regulation, and acquisition of reparative phenotypes. Volcano plot analysis demonstrated more extensive transcriptomic remodeling in infiltrating peripheral immune cells than in resident microglia. Pathway analysis identified interleukin-17 signaling as a candidate pathway associated with SCF + G-CSF treatment, along with enrichment of programs related to protein synthesis, detoxification, and glial development. Together, these findings demonstrate that the transcriptomic response to SCF + G-CSF treatment is more pronounced in cerebral monocyte/macrophage populations than in microglia, providing insight into candidate immunomodulatory mechanisms associated with brain repair in chronic TBI. - Source: PubMed
Publication date: 2026/08/06
Gaire SushilGardner Robert SKyle MicheleQiu XuechengMiller WilliamChin Lawrence SZhao Li-Ru - Leucine-rich alpha-2-glycoprotein-1 (LRG1) has received much attention as a prognostic indicator in cancer therapy where high serum levels generally predict a poor outcome. Recently, it has been shown to play an active role in cancer progression and is being pursued as a novel target in cancer therapy. LRG1 acts in neovascularization of tumors resulting in weakened blood vessels and ineffective delivery of chemotherapeutic drugs. A monoclonal antibody (mAb) against LRG1 has shown efficacy in blocking this function of LRG1, normalizing the vasculature, and improving drug delivery in mice. Extracellular LRG1 is also anti-apoptotic and promotes cell proliferation and metastasis, all through epidermal growth factor receptor family signaling. In mice, anti-LRG1 antibody therapy has been shown to inhibit these effects of extracellular LRG1 and to enhance the anti-cancer effect of immune checkpoint blockade (ICB) therapy in mice. Pre-clinical testing of the humanized version of the LRG1 mAb is underway in the United Kingdom. Intracellular LRG1 has been reported to inhibit apoptosis by blocking the binding of Cyt to apoptotic protease activating factor1 (Apaf-1) and to have other cytoplasmic functions. A nanoscale proteolysis targeting chimera (nano-PROTAC) with improved cytoplasmic delivery has been developed which enhanced apoptosis in tumors of mice. Targeting LRG1 in the aberrant angiogenesis of endothelial cells and the LRG1-Cyt -Apaf-1 axis in cancer cells, along with other putative intracellular interactions of LRG1, show potential as supplementary, if not alternative, approaches to cancer therapy. - Source: PubMed
Publication date: 2026/07/29
Jemmerson Ronald - Depression is a prevalent but underdiagnosed comorbidity in type 2 diabetes mellitus (T2DM), intensifying disease burden and complicating metabolic management. Reliable biomarkers for early detection remain limited. This study aimed to identify serum protein signatures associated with depression in individuals with T2DM using an untargeted proteomic approach. Methods Serum samples from healthy controls, T2DM patients, and T2DM patients with comorbid depression (n = 6 per group) were analyzed using LC-MS/MS-based untargeted proteomics (total n = 18). Differential protein abundance was assessed using MetaboAnalyst 6.0. Protein-protein interaction networks and pathway enrichment analyses were conducted using the STRING database. Candidate markers were further validated by ELISA in an independent cohort of healthy controls (n = 30), T2DM (n = 30), and T2DM with depression (n = 30). Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Results LC-MS/MS identified 242 serum proteins, of which 12 were significantly dysregulated among the groups. Nine proteins showed unique alterations in the T2DM-depression group. STRING analysis highlighted ST18 as a central regulatory protein. ELISA validation confirmed significant elevation of LRG1, APOC2, and ST18 in T2DM with depression compared to controls and T2DM without depression. Among these, ST18 demonstrated the highest diagnostic accuracy, yielding the greatest area under the ROC curve. Conclusion Untargeted proteomic profiling revealed distinct serum protein alterations in T2DM patients with comorbid depression. ST18 emerged as a robust and specific biomarker, suggesting its potential involvement in the molecular interplay between metabolic dysregulation and depressive pathology. Larger, longitudinal studies are required to validate its predictive utility and clarify its role in T2DM-associated depression. - Source: PubMed
Publication date: 2026/07/23
Singh JiyaBandyopadhyay SabyasachiSen AtanuKant RaviDas AnindyaSaha Sarama