GREM2

Last update 08 May 2025

Basic Info

Synonyms

CKTSF1B2, Cysteine knot superfamily 1, BMP antagonist 2, DAN domain family member 3

+ [7]

Introduction

Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.

100 Clinical Results associated with GREM2

100 Translational Medicine associated with GREM2

0 Patents (Medical) associated with GREM2

154

Literatures (Medical) associated with GREM2

01 Apr 2025·Journal of Diabetes

Association Between Circulating Gremlin 2 and β‐Cell Function Among Participants With Prediabetes and Type 2 Diabetes

Article

Author: Zhang, Yifei ; Chen, Yufei ; Gu, Yanyun ; Xu, Yu ; Wang, Jiqiu ; Lin, Xu ; Wang, Xiao ; Ni, Mengshan ; Zhu, Yinmeng ; Luo, Yaogan ; Liu, Ruixin ; Zeng, Yi Arial ; Xu, Min ; Gu, Weiqiong ; Chen, Yanru

ABSTRACTAimCirculating Gremlin 2 (Grem2) has recently been linked to human obesity, but its role in type 2 diabetes (T2D) remains unclear. This study aims to explore the association of circulating Grem2 with β‐cell function.MethodsA post hoc analysis was conducted using data from three clinical trials, in which all participants underwent the oral glucose tolerance test (OGTT). Circulating Grem2 levels were measured at 0, 1, and 2 h during the OGTT. In Trial 1, Grem2 levels were compared between participants with T2D (n = 59) and without T2D (n = 119). We further examined changes in Grem2 levels in response to oral antidiabetic drugs in participants with T2D in Trial 2 (n = 67) and calorie restriction in participants with prediabetes in Trial 3 (n = 231). The relationship between Grem2 levels and β‐cell function was analyzed across all trials.ResultsFasting and 1‐h Grem2 levels were lower in participants with T2D compared with those without T2D (728 ± 25 vs. 649 ± 31 pg/mL, p = 0.020; 631 ± 26 vs. 537 ± 31 pg/mL, p = 0.007). Fasting Grem2 levels were restored after antidiabetic treatment (550 ± 12 vs. 575 ± 12 pg/mL, p = 0.019), and 1‐h Grem2 levels increased following calorie restriction (1118 ± 89 vs. 1144 ± 90 vs. 1253 ± 89 pg/mL, p for trend = 0.002). The 1‐h Grem2 levels were positively associated with β‐cell function assessed by the oral disposition index and HOMA‐β.ConclusionReduced circulating Grem2 levels are associated with impaired β‐cell function in T2D, and could be restored through antidiabetic interventions.Trial Registration:ClinicalTrials.gov: NCT01959984, NCT01758471, NCT03856762

06 Jan 2025·International Journal of Stem Cells

Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease

Article

Author: Jin, Hye Jin ; Koh, Eun Hee ; Kim, Mi-Ok ; Ko, Myoung Seok ; Yun, Ji-Young ; Go, Sang-hyeok ; Kim, Serin

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Despite advancements in various treatments, the prevalence of DKD continues to rise, leading to a significant increase in the demand for dialysis and kidney transplantation. This study aimed to evaluate the effects of a Small cell＋Ultra Potent＋Scale UP cell (SMUP-Cell), a type of human umbilical cord blood-derived mesenchymal stem cell, on DKD in the db/db mouse model of type 2 diabetes mellitus. After administering SMUP-Cells via tail vein injection in db/db mice, the animals were monitored over a three-month period. The db/db mice exhibited an increased urine albumin-to-creatinine ratio (UACR). However, the administration of SMUP-Cells resulted in a reduction of the UACR. The expression levels of desmin, α-smooth muscle actin, and fibronectin-markers of epithelial-mesenchymal transition (EMT)-as well as kidney injury molecule 1, a sensitive marker of tubular injury, were significantly elevated in db/db mice. Treatment with SMUP-Cells ameliorated all of these changes. Notably, Gremlin isoform 2 (Grem2) exhibited the most significant difference in expression according to the transcriptome analysis. The elevated expression of Grem2 in db/db mice was significantly reduced following SMUP-Cell treatment. In vitro, treatment with high glucose and cholesterol induced Grem2 expression in renal tubular epithelial cells (RTECs), while Grem2 knockdown effectively prevented fibrosis and senescence induced by high glucose and cholesterol in RTECs. These observations suggest that SMUP-Cells inhibit the progression of DKD by inhibiting EMT through the reduction of Grem2 expression in RTECs.

01 Dec 2024·Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

Transcriptome sequencing-based study on the mechanism of action of Jintiange capsules in regulating synovial mesenchymal stem cells exosomal miRNA and articular chondrocytes mRNA for the treatment of osteoarthritis.

Article

Author: Zhongying, Chen ; Xue, Zhang ; Junbo, Zou ; Puwei, Yuan ; Yajun, Shi ; Xiaofei, Zhang

OBJECTIVETo corroborate the efficacy of Jintiange capsules (JTGs) in the treatment of osteoarthritis (OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes (SMSC-Exos) and articular chondrocytes (ACs) through transcriptome sequencing (RNA-seq).METHODSType II collagenase was used to induce OA in rats. The efficacy of JTGs was confirmed by macroscopic observation of articular cartilage, micro-CT observation, and safranin fast green staining. After SMSC-Exos and ACs were qualified, RNA-seq was used to screen differentially expressed miRNAs and mRNAs. The target genes of differentially expressed miRNAs in Synovial mesenchymal stem cells (SMSCs) were predicted based on the multiMiR R package. The co-differentially expressed genes of SMSC-Exos and ACs were obtained by venny 2.1.0. The miRNA-mRNA regulatory network was constructed by Cytoscape software. Based on the OmicShare platform, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on the mRNA regulated by key miRNAs. Expression trend analysis was performed for co-differentially expressed genes. Correlation analysis was performed on micro-CT efficacy indicators, co-differentially expressed genes mRNA and miRNA.RESULTSThe efficacy of each administration group of JTGs was significant compared with the model group. SMSC-Exos and ACs were identified by their characteristics. The expression of rno-miR-23a-3p, rno-miR-342-3p, rno-miR-146b-5p, rno-miR-501-3p, rno-miR-214-3p was down-regulated in OA pathological state, and the expression of rno-miR-222-3p, rno-miR-30e-3p, rno-miR-676, and rno-miR-192-5p expression was up-regulated, and the expression of all these miRNAs was reversed after the intervention with JTGs containing serum. The co-differentially expressed genes were enriched in the interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, etc. The expression trends of Ccl7, Akap12, Grem2, Egln3, Arhgdib, Ccl20, Mmp12, Pla2g2a, and Nr4a1 were significant. There was a correlation between micro-CT pharmacodynamic index, mRNA, and miRNA.CONCLUSIONJTGs can improve the degeneration of joint cartilage and achieve the purpose of cartilage protection, which can be used for the treatment of OA. SMSCs-related miRNA expression profiles were significantly altered after the intervention with JTGs containing serum. The 9 co-differentially expressed genes may be the key targets for the efficacy of JTGs in the treatment of OA rats, which can be used for subsequent validation.

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GREM2

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