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Gremlin 1

Gremlin, GREM1, L-D
This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010] (from NCBI)
Top mentioned proteins: BMP4, CAN, Noggin, HAD, Chordin
Papers on Gremlin
Proper Notch activity is necessary for the establishment of proximal cells and differentiation of intermediate, distal, and connecting tubule in Xenopus pronephros development.
New
Sakurai et al., In Dev Dyn, Feb 2016
In addition, when Notch signaling was overactivated at stage 20 on, intermediate, distal and connecting tubule markers, gremlin and clcnkb, were decreased while Notch downregulation increased gremlin and clcnkb.
Altered Expression of Bone Morphogenetic Protein Accessory Proteins in Murine and Human Pulmonary Fibrosis.
New
McLoughlin et al., Dublin, Ireland. In Am J Pathol, Feb 2016
We report significant increases in mRNA expression of gremlin 1, noggin, follistatin, and follistatin-like 1 (Fstl1), and significant decreases in mRNA expression of chordin, kielin/chordin-like protein, nephroblastoma overexpressed gene, and BMP and activin membrane-bound inhibitor (BAMBI).
Gremlin 2 is Repressed in Invasive Endometrial Cancer and Inhibits Cell Growth In Vitro.
New
Hirota et al., Nishinomiya, Japan. In Anticancer Res, Jan 2016
RESULTS: It was found that gremlin 2, an inhibitor of bone morphogenetic protein (BMP) signaling, was repressed in EC samples, and that gremlin 2 inhibited tumour cell growth.
Thyroid hormone receptors are differentially expressed in granulosa and cervical cells of infertile women.
New
Fernández-Real et al., Girona, Spain. In Thyroid, Jan 2016
β2 adrenergic receptor (ADRβ2) mRNA levels and the expression of genes linked to fertility such as gremlin-1 (GREM1), hyaluronan synthase 2 (HAS2), and prostaglandin-endoperoxide synthase 2 (PTGS2) were also evaluated.
Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.
Review
New
Clark et al., Fort Worth, United States. In Exp Eye Res, Dec 2015
Ocular hypertension has successfully been induced by adenovirus 5 mediated delivery of mutant MYOC, bioactivated TGFβ2, SFRP1, DKK1, GREM1, and CD44.
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
New
Impact
Wang et al., New York City, United States. In Cell, Feb 2015
We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow.
Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.
Impact
Leedham et al., New York City, United States. In Nat Med, 2015
Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1.
Canonical and noncanonical vascular endothelial growth factor pathways: new developments in biology and signal transduction.
Review
Iruela-Arispe et al., Los Angeles, United States. In Arterioscler Thromb Vasc Biol, 2015
Furthermore, ligand-independent signaling (noncanonical) has been identified through galectin and gremlin binding and upon rise of intracellular levels of reactive oxygen species.
Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors.
Stanford et al., Seattle, United States. In Clin Epigenetics, 2014
A number of top-ranked differentially methylated CpGs in genes (FDR Q-values ≤1.53E-29) were identified: C3orf14, CACNA1D, GREM1, KLK10, NT5C, PDE4D, RAB40C, SEPT9, and TRIB2, several of which had a corresponding alteration in mRNA expression.
Genetic associations with diminished ovarian reserve: a systematic review of the literature.
Review
Segars et al., New York City, United States. In J Assist Reprod Genet, 2014
RESULTS: Twenty-one articles identified genes associated with DOR: one gene mutation (FMR1), three polymorphisms (GDF9, FSHR, and ESR1), and seven genes differentially expressed between women with DOR and controls (AMH, LHCGR, IGF1, IGF2, IGF1R, IGF2R and GREM1).
The human Ah receptor: hints from dioxin toxicities to deregulated target genes and physiological functions.
Review
Bock, Tübingen, Germany. In Biol Chem, 2013
Microarray analysis of dermal cysts from a dioxin-poisoned patient revealed, in addition to induced CYP1A1, increased expression of gremlin, an antagonist of bone morphogenetic proteins.
Gremlin-mediated decrease in bone morphogenetic protein signaling promotes aristolochic acid-induced epithelial-to-mesenchymal transition (EMT) in HK-2 cells.
GeneRIF
Huang et al., Chongqing, China. In Toxicology, 2012
Gremlin 1 (a bone morphogenetic protein-7 antagonist) plays a critical role in the modulation of reno-protective action of BMP-7 in epithelial-to-mesenchymal transition.
BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation.
GeneRIF
Kamijo et al., Tokyo, Japan. In Calcif Tissue Int, 2012
The differential regulation of Gremlin2 gene expressions by BMP2 may explain the critical function of these genes during osteoblast differentiation.
Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1.
Impact
Tomlinson et al., Oxford, United Kingdom. In Nat Genet, 2012
Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus.
Deletion of Gremlin1 increases cell proliferation and migration responses in mouse embryonic fibroblasts.
GeneRIF
Brazil et al., Dublin, Ireland. In Cell Signal, 2012
Grem1 is an inhibitor of embryonic fibroblast proliferation in vitro.
Gremlin plays a key role in the pathogenesis of pulmonary hypertension.
GeneRIF
McLoughlin et al., Dublin, Ireland. In Circulation, 2012
gremlin 1 was further increased in the walls of small intrapulmonary vessels of mice during the development of hypoxic pulmonary hypertension
The role of TGF-β in the pathogenesis of primary open-angle glaucoma.
Review
Tamm et al., Regensburg, Germany. In Cell Tissue Res, 2012
The action of TGF-β2 in POAG is largely mediated through the connective tissue growth factor, whereas the activities of TGF-β1 and -β2 are modulated by the blocking effects of bone morphogenetic protein-4 (BMP-4) and BMP-7, by gremlin that inhibits BMP signaling and by several species of microRNAs.
The drumstick gene acts cell-non-autonomously and triggers specification of the small intestine in the Drosophila hindgut.
GeneRIF
Murakami et al., Yamaguchi, Japan. In Int J Dev Biol, 2010
drm is activated under the control of tll and triggers development of the small intestine cell-non-autonomously through some extracellular signaling
A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning.
Impact
Zeller et al., Basel, Switzerland. In Science, 2009
Limb development is regulated by epithelial-mesenchymal (e-m) feedback loops between sonic hedgehog (SHH) and fibroblast growth factor (FGF) signaling involving the bone morphogenetic protein (BMP) antagonist Gremlin1 (GREM1).
Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk.
Impact
Tomlinson et al., London, United Kingdom. In Nat Genet, 2008
We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1.
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