FJX1 overexpression is associated with poor prognosis and promotes gastric cancer proliferation via the PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.

Expressão do RNAm e metilação do DNA do gene DKK2 em câncer colorretal / Rnam expression and dna methylation of dkk2 gene in colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.

Pioneering studies on monogenic central precocious puberty

ABSTRACT Pubertal timing in humans is determined by complex interactions including hormonal, metabolic, environmental, ethnic, and genetic factors. Central precocious puberty (CPP) is defined as the premature reactivation of the hypothalamic-pituitary-gonadal axis, starting before the ages of 8 and 9 years in girls and boys, respectively; familial CPP is defined by the occurrence of CPP in two or more family members. Pioneering studies have evidenced the participation of genetic factors in pubertal timing, mainly identifying genetic causes of CPP in sporadic and familial cases. In this context, rare activating mutations were identified in genes of the kisspeptin excitatory pathway (KISS1R and KISS1 mutations). More recently, loss-of-function mutations in two imprinted genes (MKRN3 and DLK1) have been identified as important causes of familial CPP, describing novel players in the modulation of the hypothalamic-pituitary-gonadal axis in physiological and pathological conditions. MKRN3 mutations are the most common cause of familial CPP, and patients with MKRN3 mutations present clinical features indistinguishable from idiopathic CPP. Meanwhile, adult patients with DLK1 mutations present high frequency of metabolic alterations (overweight/obesity, early onset type 2 diabetes and hyperlipidemia), indicating that DLK1 may be a novel link between reproduction and metabolism. Arch Endocrinol Metab. 2019;63(4):438-44

Independent prognostic genes and mechanism investigation for colon cancer

PROPOSE: We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.

miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/ß-catenin signaling pathway

BACKGROUND: miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-ß signaling in vivo. However, the detailed role of miR-214 in acute kidney injury (AKI) and its underlying mechanism are still largely unknown. METHODS: In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell model were used to study AKI. The concentrations of kidney injury markers serum creatinine, blood urea nitrogen, and kidney injury molecule-1 were measured. The expressions of miR-214, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, ß-catenin, c-myc, and cyclinD1 were determined by western blot. Cell apoptosis and caspase 3 activity were evaluated by flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-214 and Dkk3. RESULTS: miR-214 expression was induced in ischemia-reperfusion (I/R)-induced AKI rat and hypoxic incubation of NRK-52E cells. Overexpression of miR-214 alleviated hypoxia-induced NRK-52E cell apoptosis while inhibition of miR-214 expression exerted the opposite effect. Dkk3 was identified as a target of miR-214. Anti-miR-214 abolished the inhibitory effects of DKK3 knockdown on hypoxia-induced NRK-52E cell apoptosis by inactivation of Wnt/ß-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/ß -catenin pathway. CONCLUSION: miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/ß -catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI.

Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression

ABSTRACT We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02–0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author's knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors.

Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice

Type 1 diabetes is an autoimmune disease caused by permanent destruction of insulin-producing pancreatic beta cells and requires lifelong exogenous insulin therapy. Recently, islet transplantation has been developed, and although there have been significant advances, this approach is not widely used clinically due to the poor survival rate of the engrafted islets. We hypothesized that improving survival of engrafted islets through ex vivo genetic engineering could be a novel strategy for successful islet transplantation. We transduced islets with adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand, which promotes beta-cell growth and differentiation, and transplanted these islets under the renal capsule of streptozotocin-induced diabetic mice. Transplantation with betacellulin-transduced islets resulted in prolonged normoglycemia and improved glucose tolerance compared with those of control virus-transduced islets. In addition, increased microvascular density was evident in the implanted islets, concomitant with increased endothelial von Willebrand factor immunoreactivity. Finally, cultured islets transduced with betacellulin displayed increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion in the presence of cytokines. These experiments suggest that transplantation with betacellulin-transduced islets extends islet survival and preserves functional islet mass, leading to a therapeutic benefit in type 1 diabetes.

Indian studies on genetic polymorphisms and cancer risk.

Genetic influences on cancer development have been extensively investigated during the last decade following publication of human genome sequence. The present review summarizes case-control studies on genetic polymorphisms and cancer risk in Indians. It is observed that the most commonly studied genes in the Indian population included members of phase I and phase II metabolic enzymes. Other than these genes, genetic polymorphisms for cell cycle and apoptosis-related factors, DNA repair enzymes, immune response elements, growth factors, folate metabolizing enzymes, vitamin/hormone receptors, etc., were investigated. Several studies also evidenced a stronger risk for combined genotypes rather than a single polymorphism. Gene-environment interaction was also found to be a determining factor for cancer development in some experiments. Data for single polymorphism and single cancer type, however, was insufficient to validate an association. It appears that much more experiments involving larger sample size, cross-tabulating genetic polymorphisms and environmental factors are required in order to identify genetic markers for different cancers in Indian populations.

Evaluación de los niveles séricos de la proteína de unión de alta afinidad de la hormona de crecimiento humana (GHBP) y del polimorfismo del exón 3 del gen del receptor de GH en niños con talla baja idiopática / Evaluation of serum levels of the high affinity binding protein of human growth hormone (GHBP) and exon 3 polymorphism of the GH receptor gene in children with idiopathic short stature

La talla baja idiopática (TBI) incluye a un grupo heterogéneo de pacientes con fallas en su crecimiento. Una causa probable de TBI puede ser la insensibilidad a la GH (IGH). La proteína de unión de GH de alta afinidad (GHBP) se genera por el clivaje proteolítico de la porción extracelular del receptor de GH (GHR) y su determinación se propone como un marcador periférico del nivel de GHR en los tejidos. El objetivo de este trabajo fue evaluar los niveles de GHBP circulantes y su asociación con factores de crecimiento y el polimorfismo del exón 3 del gen GHR en niños con TBI. Los niños con TBI presentaron talla, IMC, IGF-I, IGFBP-3, ALS y niveles de GHBP significativamente más bajos que un grupo de niños de edad comparable (p<0.001). El genotipo del exón 3 del GHR no fue un factor determinante de las diferencias observadas. La máxima respuesta de GH de los tests de estímulo de secreción correlacionó negativa y significativamente con los niveles de GHBP (r= -0.28, p= 0.012). Los perfiles de distribución de la concentración de GHBP, IGF-I, ALS y BP3 expresadas en score de desvío estándar (SDE) en la TBI, mostraron un sesgo hacia niveles bajos. En conclusión, los marcadores de acción de GH y los niveles de GHBP fueron bajos en la TBI, independientemente del genotipo del exón 3 del gen GHR. En un subgrupo de niños con TBI, niveles disminuidos de GHBP y de componentes del sistema de los IGFs, colaborarían en la evaluación de la IGH sugiriendo la búsqueda de defectos en el GHR.

Idiopathic Short Stature (ISS) includes a heterogeneous group of children with growth failure. One possible explanation for the growth failure is a reduced responsiveness to growth hormone (GH). Human circulating GH is partially bound to a highaffinity binding protein (GHBP) which is derived from proteolytical cleavage of the extracellular domain of the GH receptor. Many reports have demonstrated a close relationship between GHBP and liver GH receptor status in physiological conditions and diseases. Moreover, serum GHBP measurement has been proposed as an useful peripheral index of GH receptor abundance. Our objective was the evaluation of serum GHBP levels and its probable association with serum growth factors (IGF-I, IGFBP-3 and ALS) and the exon 3 polymorphism of the extracellular domain of the GHR gene in ISS children. Children with ISS presented significantly lower height SDS, BMI SDS, serum components of the IGFs system and GHBP concentration as compared to an age-matched control group of normal children (p<0.001). Interestingly, exon 3 genotype did not influence the differences observed in these parameters. The maximal GH response obtained after two GH provocative tests inversely and significantly correlated to GHBP serum levels (r= -0.28, p= 0.012). A frequency study showed a deviation to low SDS values of serum GHBP, IGF-I, IGFBP-3 and ALS. Conclusion: 1- in children with ISS the exon 3 genotype of the GHR gene is not a factor that could explain the lower levels observed in circulating GHBP concentration and components of the IGFs system; 2- low serum GHBP together with low IGF-I, IGFBP-3 or ALS levels would help pointing to GH insensitivity due to GH receptor gene abnormalities in ISS.

Differential Methylation Pattern of ID4, SFRP1, and SHP1 between Acute Myeloid Leukemia and Chronic Myeloid Leukemia

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.

Differential Methylation Pattern of ID4, SFRP1, and SHP1 between Acute Myeloid Leukemia and Chronic Myeloid Leukemia

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.

Aspectos moleculares da tumorigênese hipofisária: [revisão] / Molecular aspects of pituitary tumorigenesis: [review]

Os tumores hipofisários, adenomas em sua quase totalidade, são de ocorrência freqüente, representando 10 por cento a 15 por cento de todas as neoplasias intracranianas. Estas lesões são classificadas em microadenomas (< 10 mm) ou macroadenomas (> 10 mm) e como secretoras ou quiescentes (não-funcionantes). Estes tumores são capazes de secretar, de maneira autônoma, os hormônios adenohipofisários, como o hormônio de crescimento (GH), a prolactina (PRL), o hormônio adrenocorticotrófico (ACTH), o hormônio tireotrófico (TSH), o hormônio folículo estimulante (FSH) e o hormônio luteinizante (LH). A ocorrência de metástase, caracterizando um carcinoma hipofisário, é bastante rara, mas são relativamente comuns tumores de comportamento agressivo que exibem sinais de invasão local. Embora a sua patogênese ainda não seja plenamente caracterizada, muitos mecanismos moleculares envolvidos na tumorigênese hipofisária já foram desvendados. Nesta revisão, serão descritos avanços consideráveis realizados na última década relativos à compreensão dos fatores envolvidos na progressão tumoral, incluindo a participação de oncogenes, supressores tumorais e fatores de crescimento.

Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10 percent to 15 percent of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intents to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors.

Analysis of connective tissue growth factor promoter polymorphism in Thai children with biliary atresia.

OBJECTIVE: Connective tissue growth factor (CTGF) has been proposed to play a key role in the pathogenesis of hepatic fibrosis in biliary atresia (BA). The aim of the present study was to determine the single nucleotide polymorphism (SNP) in the promoter region of CTGF gene in a Thai population, and to investigate the possible role of CTGF promoter polymorphism in the susceptibility of BA. MATERIAL AND METHOD: Genomic DNA was obtained from 84 patients with BA and 142 healthy controls. The -447 G/C and -132 C/G in CTGF promoter were amplified and examined by amplification-refractory mutation system (ARMs) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The test of Hardy-Weinberg equilibrium (HWE) was performed using HWE program of SNPAnalyzer. Statistical analysis was carried out with SPSS and Epi Info. RESULT: According to the previous experiment, there were two SNPs, which were at position -447 and -132 on the promoter. However, there was only one SNP at the position -447 in the Thai population. No significant differences in genotype and allele frequency were observed between BA and controls or with BA subgroups. CONCLUSION: The present study demonstrated that CTGF polymorphism at -447 G/C was not associated with BA and the jaundice status of the postoperative BA patients.

Monocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung

Pulmonary hypertension (PH) is characterized by structural and functional changes in the lung including proliferation of vascular smooth muscle cells (VSMCs) and excessive collagen synthesis. Although connective tissue growth factor (CTGF) is known to promote cell proliferation, migration, adhesion, and extracellular matrix production in various tissues, studies on the role of CTGF in pulmonary hypertension have been limited. Here, we examined CTGF expression in the lung tissues of male Sprague Dawley rats treated with monocrotaline (MCT, 60 microgram/kg), a pneumotoxic agent known to induce PH in animals. Establishment of PH was verified by the significantly increased right ventricular systolic pressure and right ventricle/left ventricle weight ratio in the MCT-treated rats. Histological examination of the lung revealed profound muscular hypertrophy in the media of pulmonary artery and arterioles in MCT-treated group. Lung parenchyma, vein, and bronchiole did not appear to be affected. RT-PCR analysis of the lung tissue at 5 weeks indicated significantly increased expression of CTGF in the MCT-treated group. In situ hybridization studies also confirmed abundant CTGF mRNA expression in VSMCs of the arteries and arterioles, clustered pneumocytes, and infiltrated macrophages. Interestingly, CTGF mRNA was not detected in VSMCs of vein or bronchiole. In saline-injected control, basal expression of CTGF was seen in bronchial epithelial cells, alveolar lining cells, and endothelial cells. Taken together, our results suggest that CTGF upregulation in arterial VSMC of the lung might be important in the pathogenesis of pulmonary hypertension. Antagonizing the role of CTGF could thus be one of the potential approaches for the treatment of PH.

Transcription and translation of Dickkopf-1 in endometrium of pregnant mice during the peri-implantation period / 华中科技大学学报（医学）（英德文版）

To study the expression of Dickkopf-1 (DKK-1) in endometrium of pregnant mice during the peri-implantation period and the role of DKK-1 during the embryo implantation in mice. Immunohistochemical technique was employed to determine the location of DKK-1 protein in endometrium, and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was utilized to determine the levels of DKK-1 mRNA. Our results showed that the expressions of DKK1 mRNA and protein were higher in experimental groups than in control group (P<0.01) and it increased significantly on day 3 and reached its peak on day 4, and then decreased gradually on day 5-7. The levels of DKK-1 mRNA and protein on day 4 was significantly higher than those of other groups (P<0.01). It is concluded that DKK-1 probably plays an important role in signal transudation of embryo implantation and its high expression indicates the opening of implantation window.

Role of VEGF in Kidney Development, Microvascular Maintenance and Pathophysiology of Renal Disease

Vascular endothelial growth factor, VEGF, is essential for endothelial cell differentiation (vasculogenesis) and for the sprouting of new capillaries from preexisting vessels (angiogenesis). In addition, there is strong evidence that VEGF is a survival factor allowing the cells to survive and proliferate under conditions of extreme stress. Hypoxia is a key regulator of VEGF gene expression. Besides hypoxia, many cytokines, hormones and growth factors can up-regulate VEGF mRNA expression in various cell types. VEGF is present in the glomerulus of both the fetal and adult kidney. The VEGF produced by glomerular epithelial cell may be responsible for maintenance of the fenestrated phenotype of glomerular epithelial cells, thus facilitating the high rate of glomerular ultrafiltration. But there is little known about the role of VEGF in the tubule. VEGF is thought to be involved in many kinds of kidney diseases. Whereas VEGF has a beneficial role in the pathogenesis in some diseases, it does harmful action in others. Because VEGF is known to be associated with the pathogenesis of some diseases, such as diabetic nephropathy, renal tumor and polycystic kidney disease, the study about the role of VEGF is going to be a target for disease control. On the other hand, an attempt at enhancing the role of VEGF has to be made at diseases like several ARF models and experimental glomerulonephritis.