Hong Zhang

Chongqing Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (150)542.44 Total impact

  • Arthritis and Rheumatology 07/2015; DOI:10.1002/art.39268
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    ABSTRACT: IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
    Nature Communications 06/2015; 6:7270. DOI:10.1038/ncomms8270 · 10.74 Impact Factor
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    ABSTRACT: Recently, common variants within or near ATG5, which is a key autophagy gene required for the formation of autophagosomes, have been identified as a candidate gene of systemic lupus erythematosus (SLE) by several genome-wide association studies. Moreover, elevated ATG5 expression was observed in SLE as well as other autoimmune diseases. However, no significant associations between variants within ATG5 and SLE were identified in several Chinese populations. The present study was conducted to further check the genetic role of ATG5 by associating both common and rare variants of ATG5 in Chinese patients with lupus nephritis (LN), a major phenotype with poor prognosis in SLE.To detect the association of common variants of ATG5 with LN, 7 tagging single nucleotide polymorphisms (SNPs) designed in immunochip and 4 SNPs reported to be associated with SLE were genotyped in 500 LN patients and 500 healthy controls. Furthermore, direct sequencing of exons and their flanking regions in 90 LN patients, 30 SLE patients, and 60 healthy controls were performed. Functional genomic annotation was performed by using public databases.None of the 11 tagging SNPs was observed to be associated with LN. By sequencing, 13 variants were identified, including 5 common SNPs, 7 not previously described, and 1 reported as rare variants (<1%) in the Single Nucleotide Polymorphism Database or the 1000 Genome project. None of the 5 common SNPs showed significant association between patients and controls, whereas increased frequencies of rare or novel variants were observed in patients compared with healthy controls, with 6/90 in LN patients, 2/30 in SLE patients, and 1/163 in healthy controls. Although these rare variants were observed to be located in the flanking regions of exons instead of missense mutations, patients carrying them tended to have severe clinical phenotype, and in silicon analysis suggested their regulatory effects.Increased frequencies of rare variants of ATG5 were identified in patients with LN and SLE compared with healthy controls, highlighting a likely important role of rare ATG5 variants in Chinese SLE patients.
    Medicine 06/2015; 94(22):e939. DOI:10.1097/MD.0000000000000939 · 4.87 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) regulate gene expression by inhibiting transcription or translation and are involved in diverse biological processes, including development, cellular differentiation and tumor generation. miRNA microarray technology is a high‑throughput global analysis tool for miRNA expression profiling. Here, the hippocampi of four borna disease virus (BDV)‑infected and four non‑infected control neonatal rats were selected for miRNA microarray and bioinformatic analysis. Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) analysis was subsequently performed to validate the dysregulated miRNAs. Seven miRNAs (miR‑145*, miR‑146a*, miR‑192*, miR‑200b, miR‑223*, miR‑449a and miR‑505), showed increased expres-sion, whereas two miRNAs (miR‑126 and miR‑374) showed decreased expression in the BDV‑infected group. By RT‑qPCR validation, five miRNAs (miR‑126, miR‑200b, miR‑374, miR‑449a and miR‑505) showed significantly decreased expression (P<0.05) in response to BDV infection. Biocarta pathway analysis predicted target genes associated with 'RNA', 'IGF1mTOR', 'EIF2', 'VEGF', 'EIF', 'NTHI', 'extrinsic', 'RB', 'IL1R' and 'IGF1' pathways. Gene Ontology analysis predicted target genes associated with 'peripheral nervous system development', 'regulation of small GTPase-mediated signal transduction', 'regulation of Ras protein signal transduction', 'aerobic respiration', 'membrane fusion', 'positive regulation of cell cycle', 'cellular respiration', 'heterocycle metabolic process', 'protein tetramerization' and 'regulation of Rho protein signal transduction' processes. Among the five dysregulated miRNAs identified by RT‑qPCR, miR‑126, miR‑200b and miR‑449a showed a strong association with nervous system development, cell differentiation, proliferation and apoptosis.
    Molecular Medicine Reports 05/2015; DOI:10.3892/mmr.2015.3828 · 1.48 Impact Factor
  • Xu-Jie Zhou · Hong Zhang
    Rheumatology (Oxford, England) 05/2015; DOI:10.1093/rheumatology/kev118 · 4.44 Impact Factor
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    ABSTRACT: Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
    Human Molecular Genetics 04/2015; 24(13):3880-3892. DOI:10.1093/hmg/ddv128 · 6.68 Impact Factor
  • Lei Yu · Ping Hou · Ji‐Cheng Lv · Guo‐Ping Liu · Hong Zhang
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    ABSTRACT: Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and the absence of overt tubular dysfunction. Variants in solute carrier family 5 (sodium-glucose co-transporter), member 2 (SLC5A2) have been reported in FRG patients. However, the functional and expression-related consequences of such variants have been scarcely investigated. In the current study, we studied five FRG families and identified six missense mutations, including four novel variants (c.1051T>C/p.(C351R), c.1400T>C/p.(V467A), c.1420G>C/p.(A474P), c.1691G>A/p.(R564Q); RNA not analyzed) and two variants that had been previously reported (c.294C>A/p.(F98L), c.736C>T/p.(P246S); RNA not analyzed). The probands were either heterozygous or compound heterozygous for SLC5A2 variants and had glucosuria of 5.9–19.6 g/day. Human 293 cells were transfected with plasmid constructs to study the expression and function of SLC5A2 Variants in vitro. Western blotting revealed that the expression levels of SLC5A2–351R-GFP, SLC5A2–467A-GFP, SLC5A2–474P-GFP and SLC5A2–564Q-GFP were significantly decreased compared with wild-type SLC5A2-GFP (37–55%). Confocal microscopy revealed that three variants (c.1400T>C, c.1420G>C, c.1691G>A) resulted in a loss of the punctate membrane pattern typical of wild-type SLC5A2. All Variants had a significantly lower transport capacity in than the wild-type control. The current study provides a starting point to further investigate the molecular mechanism of SLC5A2 in FRG families and provides functional clues for anti-diabetes drugs.This article is protected by copyright. All rights reserved
    Human Mutation 01/2015; 36(1). DOI:10.1002/humu.22714 · 5.05 Impact Factor
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    ABSTRACT: Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.
    International Journal of Molecular Sciences 01/2015; 16(8):19347-68. DOI:10.3390/ijms160819347 · 2.86 Impact Factor
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    ABSTRACT: To retrospectively evaluate the HER2 status of 1 501 invasive breast cancer (IBC) by immunohistochemistry (IHC) and fluorescent in situ hybridizaion (FISH), and to compare and analyze the changes and their effects, using the 2007 and 2013 American Society of Clinical Oncology/College of American Pathologist(ASCO/CAP) HER2 testing guidelines. Tissue handling and HER2 testing were performed according the 2007 ASCO/CAP guideline recommendations. The HER2 status of all newly diagnosed IBC were routinely assessed by IHC, and reflex FISH assay was done on all the IHC equivocal (IHC 2+) cases. The HER2 status of 1 501 cases of IBC was re-evaluated according to these two criteria. Using the 2007 and 2013 ASCO/CAP criteria, the overall positive, equivocal and negative rates of HER2 over-expression and/or amplification in the 1 501 IBCs were 23.05% and 23.52%, 11.59% and 12.52%, and 65.36% and 63.96%, respectively. The positive and equivocal rates increased by 0.47% and 0.93% respectively, but the negative rate decreased by 1.40% when using the new criteria. For HER2 IHC staining using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 17.99% and 18.13% (+0.13%), 32.51% and 32.91% (+0.40%) and 49.50% and 48, 97% (-0.53%), respectively. FISH for HER2 amplification was done in 348 of the 1 501 IBCs, and using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 27.59% and 29.02% (+1.43%), 1.15% and 3.74% (+2.59%) and 71.26% and 67.24% (-4.02%), respectively. The application of 2013 ASCO/CAP guideline could lead to an increase in positive and equivocal rates, and a decrease in negative rate. The influence could be more prominent for the evaluation of FISH result, and would raise the positive and equivocal rates since a mean HER2 copy number is used in the new criteria. Our re-estimation of IHC result was concordant with the prediction of the guideline.
    Zhonghua bing li xue za zhi Chinese journal of pathology 01/2015; 44(1):42-47.
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    ABSTRACT: To evaluate the value of ultrasound (US) in predicting axilla status and to investigate the clinic pathologic characters in the axillary node metastasis. From June 2012 to June 2013, 323 female primary breast cancer patients who received both axilla ultrasound and pathology examinations were reviewed retrospectively. The features of axillary nodes including diameter, longitudinal-transverse axis ratio, cortical thickness and blood flow grade were used to evaluate axillary status. US accuracy of axillary node metastasis was analyzed correlated with the final pathology results. The clinical and histological features associated with axillary node metastasis was analyzed by χ(2) test. The proportions of Luminal A-like, Luminal B-like, human epidermalgrowth factor receptor-2 positive and triple negative breast cancer were 11.1% (36/323), 58.5% (189/323), 13.3% (43/323) and 17.0% (55/323) . The sensitivity, specificity, positive predictive value and negative predictive value of axilla US in the diagnosis of nodal metastasis were 35.6% (46/129), 98.9% (181/183), 95.8% (46/48) and 68.6% (181/264). Axillary lymph node metastasis had statistically significant correlation with menopausal status and clinical tumor size (χ(2) = 4.337, 11.100; P = 0.037, 0.001). Standardized ultrasound is the basic way to evaluate axilla status. Sentinel lymph node biopsy should be done to acquire accurate preoperative staging of axilla when US shows no signs of metastasis. Axillary lymph node metastasis is significantly related to menopausal status and clinical tumor size, but not significantly related to subtype classification of primary breast cancer.
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    ABSTRACT: Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV) was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.
    International Journal of Molecular Sciences 12/2014; 15(12):21825-21839. DOI:10.3390/ijms151221825 · 2.86 Impact Factor
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    ABSTRACT: Abstract We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
    Nature Genetics 10/2014; DOI:10.1038/ng.3118 · 29.65 Impact Factor
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    ABSTRACT: Objective Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome-wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis. Methods In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. ResultsIn addition to associations with HLA gene polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19-2.19], P = 2.07 x 10(-3)) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, P = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower MTMR3 transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients. Conclusion Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.
    Arthritis and Rheumatology 10/2014; 66(10). DOI:10.1002/art.38749
  • Ling Xin · Hong Zhang · Shuang Zhang · Jingming Ye · Ting Li · Yinhua Liu
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    ABSTRACT: Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q23 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN.
    Journal of the American Society of Nephrology 09/2014; 26(5). DOI:10.1681/ASN.2014010096 · 9.47 Impact Factor
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    ABSTRACT: The cingulum and fornix play an important role in memory, attention, spatial orientation and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc), hippocampal part of the cingulum (cgh) and fornix (fx) were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE) algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2-year-old followed by a slow increase to 25-year-old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network (DMN) was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with mental disorders.
    Frontiers in Aging Neuroscience 08/2014; 6:228. DOI:10.3389/fnagi.2014.00228 · 2.84 Impact Factor
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    ABSTRACT: Objective Human neutrophil peptides (HNP) were recently implicated in the neutrophil extracellular trap (NET) complex, the impaired degradation of which has been associated with lupus nephritis (LN).Methods Forty LN patients, 40 SLE patients without kidney injury, 63 immunoglobulin A nephropathy (IgAN) patients, 20 minimal change disease (MCD) patients and 33 healthy controls were included in the present study. LN, IgAN and MCD patients were diagnosed with renal biopsy. LN patients were followed for a median period of 5.5 years. Clinical and laboratory data at the time of renal biopsy and follow-up were collected for each LN patient. Serum levels of HNP1–3 were measured with enzyme-linked immunosorbent assay.ResultsSerum HNP1-3 levels in LN patients were significantly higher than for SLE patients without kidney injury (P < 0.001), IgAN patients (P = 0.012), MCD patients (P = 0.010) and healthy controls (P = 0.022). Serum HNP1–3 levels were an independent indicator of LN (P = 0.006, OR = 7.5, 95% CI, 1.782–31.842), were statistically correlated with urinary protein excretion (P = 0.009) and activity index (P = 0.042) and were only marginally correlated with neutrophils (P = 0.054) and white blood cell counts (P = 0.051). Serum levels of HNP1–3 were a predictor of proteinuria remission after correction for multiple parameters (multivariate hazard 0.209; 95% CI 0.046–0.951; P = 0.043).Conclusions The data from this study indicated that HNP1–3, one component of the NET, is a potential biomarker for LN.
    International Journal of Rheumatic Diseases 08/2014; 18(5). DOI:10.1111/1756-185X.12433 · 1.77 Impact Factor
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    ABSTRACT: Background Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration. Methods Initially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF/sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor (sFlt-1) was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN. Results VEGF/sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers (0.33±0.27 vs. 0.43±0.22, p = 0.02) in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated (101.18±25.19 vs. 79.73±18.85 pg/ml, p<0.001), but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients (93.40±39.78 vs. 71.92±15.78 pg/ml, p<0.001). Plasma sFlt-1 levels in IgAN patients correlated with proteinuria (severe (>3.5 g/d) vs. moderate (1–3.5 g/d) vs. mild (<1 g/d) proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg/ml; severe vs. mild: p<0.001, moderate vs. mild p = 0.001, severe vs. moderate: p = 0.014), hypertension (with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg/ml, p = 0.015) and vWF levels (r = 0.161, p = 0.021). Conclusions The present study found elevated sFlt-1 in IgAN patients and further identified its correlation with proteinuria, hypertension and vWF levels. These results suggested that elevated sFlt-1 contributes to endothelial injury in IgAN.
    PLoS ONE 07/2014; 9(7):e101779. DOI:10.1371/journal.pone.0101779 · 3.23 Impact Factor
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    ABSTRACT: Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma (CRC). In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution. Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Trans-well assays. Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of β-catenin (p<0.001). In addition, NAT10 membrane staining reflected depth of invasion and tendency to metastasize (all P values <0.001), and was associated with poorer prognosis (P=0.023). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility. Conclusions: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is thus correlated with invasive potential and poorer clinical outcome. This suggests NAT10 may be a useful prognostic marker and potential therapeutic target in CRC.
    Clinical Cancer Research 06/2014; 20(17). DOI:10.1158/1078-0432.CCR-13-3477 · 8.19 Impact Factor
  • Xinying Jia · Hong Zhang · Xu Cao · Yuxin Yin · Bo Zhang
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    ABSTRACT: The airway epithelium is exposed to a range of irritants in the environment that are known to trigger inflammatory response such as asthma. Transient receptor potential vanilloid 1 (TRPV1) is a Ca(2+)-permeable cation channel critical for detecting noxious stimuli by sensory neurons. Recently increasing evidence suggests TRPV1 is also crucially involved in the pathophysiology of asthma on airway epithelium in human. Here we report that in airway epithelial cells TRPV1 activation potently induces allergic cytokine thymic stromal lymphopoietin (TSLP) release. TSLP induction by protease-activated receptor (PAR)-2 activation is also partially mediated by TRPV1 channels.
    FEBS Letters 06/2014; 588(17). DOI:10.1016/j.febslet.2014.06.018 · 3.34 Impact Factor

Publication Stats

2k Citations
542.44 Total Impact Points

Institutions

  • 2014–2015
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
    • Beijing Zoo
      Peping, Beijing, China
  • 2003–2015
    • Peking University
      • Institute of Urology
      Peping, Beijing, China
  • 1999–2015
    • Beijing Medical University
      • • Department of Medicine
      • • Department of Respiratory Medicine
      • • Institute of Nephrology
      • • Department of Internal Medicine
      Peping, Beijing, China
  • 2013–2014
    • Peking University Health Science Center
      Peping, Beijing, China
    • Peking Union Medical College Hospital
      • Department of Rheumatology
      Peping, Beijing, China
  • 2008–2012
    • Anhui Medical University
      • Department of Pathology
      Luchow, Anhui Sheng, China
    • Shanghai's Children's Medical Center
      Shanghai, Shanghai Shi, China
  • 2007
    • University of Science and Technology of China
      • Department of Physics
      Hefei, Anhui Sheng, China
  • 2000–2002
    • Okayama University
      • Department of Medicine and Clinical Science
      Okayama, Okayama, Japan