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High PITX2 expression was observed in non-functional pituitary neuroendocrine tumors with cavernous sinus invasion, suggesting that PITX2 may be involved in cavernous sinus invasion of pituitary neuroendocrine tumors
the present report is the first to associate a gain-of-function mutation of PITX2c with increased vulnerability to AF, therefore, restoration of normal PITX2c function may be a potential therapeutic target in AF patients.
spontaneous diastolic depolarization observed in atrial myocytes with TBX5-deletion can be explained by altered intracellular calcium handling and suppression of inward-rectifier potassium current.
Study found no association between PITX2 rs2595104 and increased risk of atrial fibrillation.
the increased frequency in PCG patients of rare FOXC2 and PITX2 variants with mild functional alterations, suggests they play a role as putative modifier factors in this disease further supporting that Congenital glaucoma (CG) is not a simple monogenic disease and provides novel insights into the complex pathological mechanisms that underlie CG.
Truncations may be the primary mutation type in PITX2. Glaucoma onset may be earlier in patients with mutations in PITX2 than in those without mutations in PITX2 and FOXC1. A block of the anterior chamber angle by the end of the iris might represent the main factor influencing the development of glaucoma in ARS patients with an asymmetric aniridia phenotype.
Paired-like homeodomain transcription factor 2 (PITX2)frameshift mutation was identified in a Chinese Han family three affected individuals with Axenfeld-Rieger syndrome.
These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.
We observed no association between common genetic variants in PITX2 and IL6 and atrial tachycardia in infants after congenital heart disease surgery.
Heterozygous pathogenic variants in the PITX2 and FOXC1 genes accounted for 66% (6/9) of the ARS/ASD cases. The absence of PAX6 or CYP1B1 abnormalities could reflect our small sample size, although their analysis could be justified in ARS/ASD patients that present with congenital glaucoma or aniridia.
Our results suggest a prognostic role of PITX2 promoter methylation in colorectal cancer
These data further support the link between PITX2 and the WNT pathway and suggest a new role in regulation of collagen gene expression during development.
Single Nucleotide Polymorphism in PITX2 gene is associated with inflammation in acute appendicitis.
PITX2 has been implicated in determination of right-left symmetry during development. Anomalies in organ arrangement have been linked to increased prevalence of gastrointestinal and intra-abdominal complications, which may explain the effect of rs2129979 on appendicitis risk.
Minor allele of SNP rs2200733 is associated with the risk of preeclampsia. SNP rs220073 may represent a common risk factor that predispose women to develop both preeclampsia during pregnancy and cardiovascular disease later on.
This study for the first time demonstrates that the PITX2 mutation could lead to non-syndromic orodental anomalies in humans. We propose that the specific location in the C-terminal domain of PITX2 is exclusively necessary for tooth development.
Rs17042171, near PITX2 on chromosome 4q25, is associated with atrial fibrillation susceptibility in the Chinese Han population from the central plains, suggesting that this SNP can provide a new strategy for clinical diagnosis in atrial fibrillation patients.
NMR methodology was employed for determining the dynamics of lysine side-chain amino groups via (15)N relaxation measurements in the Lys50-class homeodomains from the Drosophila protein Bicoid and the human protein Pitx2
Results demonstrate that BBP decreases endometrial mesenchymal stem/stromal cell (EN-MSC) myogenic differentiation through up-regulation of miR-137 and decreased transcription of PITX2. Also, BBP affects PITX2 expression through miR-137 targeting the 3' untranslated region of PITX2 mRNA.
For non-metastatic triple-negative breast cancer patients, selective determination of the PITX2 DNA-methylation status may serve as a cancer biomarker for predicting response to anthracycline-based adjuvant chemotherapy.
the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells.
Studies demonstrate that the homeodomain transcription factor Pitx2 has a postmitotic role in maintaining skeletal muscle integrity and energy homeostasis in fetal muscle fibers.
Using Pitx2/3 single and double mutant mice that provide genetic models of deregulated redox states, we demonstrate that moderate overproduction of ROS results in premature differentiation of satellite cells while high levels lead to their senescence and regenerative failure
The paper's findings reveal a role for Pitx2 in maintaining proper cardiac cellular composition during heart regeneration via the maintenance of proper mitochondrial structure and function.
data demonstrate that HTD, but not HTN, can impair Pitx2>>Wnt pathway providing thus a molecular link to AF
Defined a transcriptional architecture for atrial rhythm control organized as an incoherent feed-forward loop, driven by TBX5 and modulated by PITX2. TBX5/PITX2 interplay provides tight control of atrial rhythm effector gene expression, and perturbation of the co-regulated network caused atrial fibrillation susceptibility.
Pitx2 is essential to maintain iHepSCs stem cell characteristics
Uncovering a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates dental epithelial stem cells homeostasis and dental development.
Study reports that p27 normally exerts a negative feedback on p21 expression: p27 directly represses the expression of the transcription factor Pitx2 which in turn maintains decreased p21 levels. Consequently, in cells lacking p27, de-repression of Pitx2 causes the up-regulation of p21 showing a new mechanism by which p27 regulates cell cycle progression by transcriptionally regulating the expression of Pitx2 and p21.
demonstrate a dose-dependent relation between Pitx2 expression and the expression of atrial fibrillation susceptibility genes
Data suggest a putative role of the homeobox protein PITX2 (PITX2B) isoform during ventricular septation as well as in the maturation of the right portion of the atrioventricular canal.
Pitx2 represses left-side expression of a conserved lncRNA Playrr. Pitx2 auto-regulation directs chromatin topology to coordinate left-right transcription and organogenesis.
The AP-2beta transcription factor is an important effector of PITX2 function during corneal development, required for differentiation of corneal endothelium and establishment of angiogenic privilege.
Pitx2-deficient neonatal mouse hearts failed to repair after apex resection, whereas adult mouse cardiomyocytes with Pitx2 gain-of-function efficiently regenerated after myocardial infarction
This study describes a Pitx2-miRNA pathway controlling cell proliferation in myogenic cells, providing new targets to enhance the regenerative capacity of limb skeletal-muscle myogenic precursor cells for the treatment of skeletal-muscle diseases.
de-regulation of both PITX2 and ENPEP could contribute to an increased risk of atrial fibrillation in carriers of disease-associated variants.
Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine
Pitx2c may regulate functional Left-Right asymmetry of the developing limb.
The combination of Pitx2, a regulator of dental stem cells and miR-200a converts mesenchymal cells to a fully differentiated dental epithelial cell type.
Pitx2 has genetically separable postnatal and developmental functions, unveil direct Pitx2 target genes that include channel and calcium handling genes, as well as genes that stabilize the intercalated disc in postnatal atrium.
Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration.
Late zygotic oep mutants have strongly reduced or absent pitx2 expression in the lateral plate mesoderm (LPM), but this expression can be rescued to strong levels by restoring oep in midline structures only.
asymmetric expression of fatty acid elongase 6 gene is controlled by left right Nodal signaling and is independent of Pitx2 function in zebrafish
This study found PITX2 to be decreased in patients with sustained Atrial Fibrillation, suggesting a PITX2 loss of function mechanism in Atrial Fibrillation.
Antagonism between Nodal and Pitx2c activities sets an upper limit on parapineal cell numbers. Restricting parapineal cell number is crucial for the correct elaboration of epithalamic asymmetry.
Pitx2, implicated in left-right asymmetry, possessed appropriate 'atypical' Pegasus binding sites in its promoter.
Data indicate that retinoic acid (RA) induces the expression patterns of genes normally expressed in the posterior tooth-forming region, such as pitx2 and dlx2b.
Pitx2 is essential for proper eye and craniofacial development in zebrafish.
Retinoic acid regulation of pitx2 is essential for coordinating interactions among neural crest, mesoderm, and developing eye.
Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2
ESR1 inhibits the expression of Pitx2 gene by binding to a left side-specific enhancer region in Pitx2 gene and recruiting histone deacetylase 1 to this region, leading to the suppression of Pitx2 gene in the left lateral plate mesoderm.
A novel spliced variant of cattle PITX2 was identified. In addition, a 24bp deletion detected in the PITX2 gene was found to have significant associations with cattle growth traits.
This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described.
ALL1-responsive protein ARP1
, all1-responsive gene 1
, homeobox protein PITX2
, paired-like homeodomain transcription factor 2
, pituitary homeobox 2
, rieg bicoid-related homeobox transcription factor 1
, BRX1 homeoprotein
, orthodenticle-like homeobox 2
, paired-like homeodomain transcription factor Munc 30
, paired-like homeodomain transcription factor 2a
, homeodomain transcription factor 2
, transcription factor Pitx2
, homeodomain transcription factor Pitx2