Ask about this productRelated genes to: GREM2 antibody
- Gene:
- GREM2 NIH gene
- Name:
- gremlin 2, DAN family BMP antagonist
- Previous symbol:
- -
- Synonyms:
- Prdc, FLJ21195, CKTSF1B2, DAND3
- Chromosome:
- 1q43
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-30
- Date modifiied:
- 2014-11-19
Related products to: GREM2 antibody
Related articles to: GREM2 antibody
- Therapeutic mesenchymal stromal cells (MSCs) promote healing in severe injuries like skin burns. However, expansion on stiff culture surfaces activates MSCs into scar-promoting myofibroblasts. We previously introduced 'mechanical memory' to describe how MSCs primed on scar-stiff surfaces retain myofibroblast traits even after switching to softer, skin-like surfaces. Now, we identify mechanisms and factors that suppress myofibroblast activation during priming in soft cultures. These 'soft memory' factors are poised to preserve MSC regenerative features while preventing fibrogenesis. Mechanically primed MSCs were compared via RNA- and ATAC-sequencing to co-analyze gene transcription and chromatin accessibility. Highly accessible promoters of genes upregulated after soft priming, which retained this pattern after transitioning to stiff surfaces, were enriched for HOXA11 transcription factor binding motifs. Knocking down HOXA11 increased osteogenic gene expression in soft-primed MSCs and reduced anti-fibrotic factors, including the transcription factor SALL1, which suppresses pro-fibrotic genes like Postn, Col8a1, Grem2, Thbs1, Thbs2, and Gata6. We identify GATA6 as a keeper of stiff-induced myofibroblast memory after switching to soft surfaces. Manipulating the SALL1-GATA6 circuit yielded therapeutic MSCs that suppressed fibrosis in a hypertrophic skin-scarring animal model. Therefore, controlling myofibroblast memory could improve MSC-based organ repair therapies. - Source: PubMed
Publication date: 2026/04/22
Younesi Fereshteh SadatMiller Andrew EDiao LiGuo XinyingAndonian NatalieKarimizadeh ElhamBarker Thomas HHinz Boris - Pulmonary hypertension (PH) underscores the urgent need for novel therapeutic targets. This study aimed to employ a proteome-wide Mendelian randomization (MR) approach to systematically identify circulating proteins causally associated with PH, thereby providing genetically validated candidate targets for drug development. We adopted a 2-sample MR design, integrating large-scale plasma proteomic quantitative trait loci (pQTL) data (encompassing 4148 proteins) and summary statistics from a large-scale PH genome-wide association study (2047 cases, 8301 controls). Candidate targets were screened through a multilayered analytical pipeline comprising proteomic MR, transcriptomic MR, and summary-data-based Mendelian randomization. The ultimately identified MR-Identified Causal Candidate Targets (MR-ICTs) underwent rigorous Bayesian colocalization analysis, followed by biological characterization through functional enrichment analysis, single-cell transcriptomics, and phenome-wide association studies. Through robust genetic causal inference, this study provides that circulating proteins such as LYZ, GREM2, NID1, and PF4V1 play causal roles in PH pathogenesis. These findings offer a set of rigorously genetically validated, high-priority therapeutic targets for developing novel PH treatments, specifically addressing key pathological mechanisms such as innate immunity, BMP signaling pathway dysregulation, and platelet activation. Our multi-dimensional analysis ultimately identified 6 MR-ICTs causally associated with PH. Notably, the causal associations for lysozyme C (LYZ), gremlin-2 (GREM2), nidogen-1 (NID1), and platelet factor 4 variant 1 (PF4V1) were stringently validated by Bayesian colocalization analysis (posterior probability for hypothesis 4 [PPH4], indicating a shared causal variant, > 0.99). Functional enrichment analysis revealed significant involvement of these targets in immune response and TGF-β signaling pathways. Single-cell analysis further elucidated their cell-type-specific expression, with LYZ predominantly expressed in monocytes and PF4V1 almost exclusively in platelets. - Source: PubMed
Wu ChaolingZhao WenboZhu XiaojingLi YuanbinChen ZhihongYan Xu - Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Although diagnostic and therapeutic strategies have advanced, the molecular mechanisms driving CRC pathogenesis are not fully understood, highlighting the need for novel biomarkers and therapeutic agents. - Source: PubMed
Publication date: 2026/01/08
Liao QimingXue YulongYu YajiangLiu MengzheYu ZeyuanCheng XiaoxiaZhang LeiJi Xinying - Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder influenced by genetic, environmental, and immunological factors. Current treatment primarily relies on thyroid hormone replacement therapy, yet the underlying mechanisms of the disease and its response to therapy remain poorly understood. Therefore, elucidating the molecular mechanisms of HT, especially in response to immunosuppressive agents, is essential for improving therapeutic strategies. In this study, we integrated transcriptomic profiling, machine learning, and experimental validation to elucidate the immunoregulatory effects of Dex in HT. Peripheral blood samples from healthy individuals, untreated HT patients, and Dex-treated HT patients were analyzed via RNA sequencing, with differentially expressed genes (DEGs) identified using the "limma" R package. Functional enrichment analyses (GO, KEGG, and GSEA) revealed that Dex treatment downregulated key immune and inflammatory pathways, particularly those involving cytokine signaling and the JAK-STAT axis. Integrative machine learning approaches (LASSO, SVM-RFE, and Random Forest) consistently identified GREM2 as a Dex-responsive gene, which was further validated in an independent cohort using correlation and ROC analyses, supporting its predictive value for treatment response. CIBERSORT analysis demonstrated substantial alterations in immune cell infiltration, including shifts in B-cell subtypes. Mechanistically, GREM2 was validated as a downstream target of STAT3 through dual-luciferase assays and siRNA interference. In vitro studies using LPS-induced Nthy-ori 3-1 thyroid cells confirmed that Dex exerts its anti-inflammatory effects by inhibiting STAT3 phosphorylation, thereby reducing GREM2 expression and downstream proinflammatory cytokines such as TNF-α, IL-1β, and CCL2. These findings highlight the STAT3/GREM2 signaling axis as a critical mediator of Dex's therapeutic action in HT and provide a mechanistic framework for its potential clinical application in autoimmune thyroid diseases. - Source: PubMed
Publication date: 2025/11/13
Zeng HuarongChen YingjieHu TianchiZhou YiSu MeimeiLin LinKe Zhifu - : Joint hypermobility (JH) is an increase in the range of joint movements beyond physiological limits. To date, there is no common understanding of the pathogenesis of this condition. The aim of the study was to analyze the intergenic interactions of SNPs of candidate genes involved in connective tissue metabolism in order to assess their total contribution to the pathogenesis of JH. : A single-stage cross-sectional study was conducted with the participation of 181 healthy young men (N = 54) and women (N = 127); the average age was 21.86 ± 0.22 years. JH was determined by the Beighton scale (1998). SNPs of the , , , , and genes were identified. The analysis of gene-gene interactions was carried out using the MDR and GeneMANIA.org, and protein-protein interactions were analyzed using STRING. : Models of intergenic interactions were constructed: a one-factor model (rs11144134 ()) and a three-factor model (rs229077 and rs9978597 of the gene and rs11144134 of the gene), with the identification of risky genotypes. In addition, the possible mechanisms of intergenic interaction were predicted. Interaction at the level of expression products was found for and , and with the expansion of the network, possible functional partner genes such as , , and were discovered. : Models of intergenic interactions were constructed, a one-factor model and a three-factor model, and the risk genotypes were identified. Rs11144134 of the gene can be considered a promising new marker of JH. - Source: PubMed
Publication date: 2025/10/07
Akhiiarova KarinaTyurin AntonKhusainova Rita