Ying Fan

Icahn School of Medicine at Mount Sinai, Borough of Manhattan, New York, United States

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Publications (19)72.17 Total impact

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    ABSTRACT: BAMBI acts as a pseudoreceptor for the TGFβ type I receptor family and negative modulator of TGFβ kinase signaling and BAMBI(-/-) mice show mild endothelial dysfunction. As diabetic glomerular disease is associated with TGFβ overexpression and microvascular alterations, we examined the effect of diabetes on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in glomeruli from mice with type 2 DM, BAMBI was downregulated. We then examined the effects of BAMBI deletion on streptozotocin- induced diabetic glomerulopathy in mice. BAMBI(-/-) mice developed more albuminuria with widening of foot processes than BAMBI(+/+) mice along with increased activation of alternative TGFβ pathways such as ERK-1/2 and Smad1/5 in glomeruli and cortex of BAMBI(-/-) mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability, were downmodulated in glomeruli from DM BAMBI(-/-) mice. Incubation of glomeruli from non-diabetic BAMBI(+/+) or BAMBI(-/-) mice with TGFβ resulted in downregulation of Vegfr2 and Angpt1, effects that were more pronounced in BAMBI(-/-) mice and prevented by a MEK inhibitor. The downregulation of Vegfr2 in DM was localized to glomerular endothelial cells using a histone yellow reporter under the Vegfr-2 promoter. Thus BAMBI modulates effects of diabetes on glomerular permselectivity in association with altered signaling of ERK1/2 and Smad1/5. Thus, BAMBI modulates effects of diabetes on glomerular permselectivity in association with altered ERK1/2 and Smad1/5 signaling. Future therapeutic interventions with inhibitors of alternative TGFβ signaling may therefore be of interest in DM nephropathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 01/2015; 64(6). DOI:10.2337/db14-1397 · 8.47 Impact Factor
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    ABSTRACT: Homeodomain interacting protein kinase 2 (HIPK2) functions as either a co-repressor or a co-activator of transcriptional regulators. Dysregulation of HIPK2 is associated with cancer and neurological disease. Recently, we found that HIPK2 is also an important driver of kidney fibrosis in the HIV-1 transgenic murine model, Tg26. HIPK2 protein levels are upregulated in the tubular epithelial cells of Tg26 mice as well as in kidney biopsies of patients with HIV-associated nephropathy, focal segmental glomerulosclerosis, diabetic nephropathy, and IgA nephropathy. We found that HIPK2 regulates pro-apoptotic, pro-fibrotic, and pro-inflammatory pathways including p53, transforming growth factor p (TGF-beta)-SMAD family member 3 (Smad3), Notch, Wingless and INT-1 (Wnt)/beta-catenin, and nuclear factor kappa-light-chain-enhancer of activated B cells in renal tubular epithelial cells. Our data suggest that HIPK2 may be a potential target for antifibrotic therapy. As mice with germline deletion of HIPK2 do not exhibit any phenotypic change under basal conditions, we do not expect significant side effects with specific HIPK2 inhibitors. However, potential effects of HIPK2 on tumor growth should be considered because of its tumor suppressor effects. Therefore, further understanding of structure-function relationships and post-translational modifications of HIPK2 are necessary to develop more specific drugs targeting the pro-fibrotic effects of HIPK2.
    11/2014; 4(1):97-101. DOI:10.1038/kisup.2014.18
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    ABSTRACT: Diabetic retinopathy (DR) is a common complication of diabetes. DR obstructs blood supply to the retina and has serious and long-lasting detrimental effects on quality of life. Panretinal photocoagulation, a laser surgical intervention, is advocated for early treatment of DR to prevent visual loss; however, results from studies reporting its efficacy vary markedly. In this review, we systematically conducted a database search of randomized controlled trials that investigated the safety and efficacy of different types of laser interventions, alone or in combination with adjunct intravitreal steroid utilization, in patients with DR. Data from 14 studies demonstrated that panretinal photocoagulation can be a safe and effective option for reducing visual loss and blindness in patients with DR.
    Expert Review of Medical Devices 08/2014; DOI:10.1586/17434440.2014.953057 · 1.78 Impact Factor
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    ABSTRACT: Profiling of temporal changes of gene expression in the same kidney over the course of renal disease progression is challenging because repeat renal biopsies are rarely indicated in clinical practice. Here, we profiled the temporal change in renal transcriptome of HIV-1 transgenic mice (Tg26), an animal model for human HIV-associated nephropathy (HIVAN), and their littermates at three different time points (4, 8, and 12 weeks of age) representing early, middle, and late stages of renal disease by serial kidney biopsy. We analyzed both static levels of gene expression at three stages of disease and dynamic changes in gene expression between different stages. Analysis of static and dynamic changes in gene expression revealed that up-regulated genes at the early and middle stages are mostly involved in immune response and inflammation, whereas down-regulated genes mostly related to fatty acid and retinoid metabolisms. We validated the expression of a selected panel of genes that are up-regulated at the early stage (CCL2, CCL5, CXCL11, Ubd, Anxa1, and Spon1) by real-time PCR. Among these up-regulated genes, Spon1, which is a previously identified candidate gene for hypertension, was found to be up-regulated in kidney of human with diabetic nephropathy. Immunostaining of human biopsy samples demonstrated that protein expression of Spon1 was also markedly increased in kidneys of patients with both early and late HIVAN and diabetic nephropathy. Our studies suggest that analysis of both static and dynamic changes of gene expression profiles in disease progression avails another layer of information that could be utilized to gain a more comprehensive understanding of disease progression and identify potential biomarkers and drug targets.
    PLoS ONE 03/2014; 9(3):e93019. DOI:10.1371/journal.pone.0093019 · 3.53 Impact Factor
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    ABSTRACT: Background and aims: The present study was designed to characterize and compare the ambulatory blood pressure changes of patients with Type 2 diabetic nephropathy (DN) and non-diabetic chronic kidney disease (CKD), and to investigate the features of ambulatory blood pressure in patients with Type 2 diabetic nephropathy (DN) in comparison with those of non-diabetic chronic kidney disease (CKD) in our medical center. Materials and methods: 62 patients with Type 2 diabetic nephropathy (DN) in compliance with the diagnosis criteria of CKD were enrolled in the study, without renal replacement therapy. Their 24-h ambulatory blood pressure monitoring (ABPM) results were observed and compared with the ambulatory blood pressure results of 152 non-diabetic CKD patients with matching age, sex, renal function and other aspects. Results: Analysis of ABPM data from 62 patients with Type 2 DN and 152 patients with nondiabetic CKD indicated: 1. The average 24-h systolic blood pressure (SBP), daytime and nighttime systolic blood pressure (SBP) in the patients with DN were all significantly higher than those of patients with non-DN. 2. Blood pressure variability did not differ considerably between the two groups; nighttime blood pressure decline was small in both groups, but not significantly different. 3. The systolic blood pressure loads in the patients with DN were all significantly higher than those of patients with non-DN. 4. The prevalence of abnormal Circadian BP rhythm was 90.3% in patients with DN, which did not differ considerably from the patients with non-DN represented by 81.6%. 5. The nighttime SBP was correlated with 24-h urinary protein in patients with both non-DN and DN. Conclusions: Systolic blood pressure control of patients with intermediate or advanced diabetic nephropathy was worse than that of patients with non-diabetic CKD, and non-dipping rhythm was quite common. The nighttime SBP correlated with 24-h urinary protein excretion.
    Clinical nephrology 10/2012; 79(3). DOI:10.5414/CN107401 · 1.23 Impact Factor
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    ABSTRACT: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy. Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005). These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.
    PLoS ONE 05/2012; 7(5):e36041. DOI:10.1371/journal.pone.0036041 · 3.53 Impact Factor
  • Dawei Luo, Ying Fan, Xun Xu
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    ABSTRACT: The accumulation of advanced glycated end products (AGEs) in retinal blood vessels is one of the major etiological factors contributing to diabetic retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors of AGEs formation. The aim of this study was to investigate whether AG could protect the development of diabetic retinopathy through inhibition of AGEs. Rat diabetes was induced by intraperitoneal injection with streptozotocin (STZ). AG was given to rats in drinking water. Retina was extracted 3 and 6 months following STZ and AG administration. Immunochemistry and transmission electron microscope were used to detect the expression of AGEs and retina morphology. Extensive staining of AGEs was detected in retinal blood vessels of 3- and 6-month diabetic rats, while no significant staining was found in the control non-diabetic retina or AG treated groups. Pericyte loss, endothelial cell proliferation, increased ratio of endothelial cells/pericytes, acellular capillaries and capillary occlusion were observed in the retina of 6-month diabetic rats. The increased electron density of retinal capillary basement membrane, mitochondrial swelling in pericytes and endothelial cells were also found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats did not have similar morphological changes compared to control group. The AGEs staining in AG-treated rats was still weakly positive. AGEs plays pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal microvasculature changes. AG could prevent the onset and development of diabetic retinopathy through inhibition of AGEs.
    Bioorganic & medicinal chemistry letters 05/2012; 22(13):4386-90. DOI:10.1016/j.bmcl.2012.04.130 · 2.33 Impact Factor
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    ABSTRACT: Kidney fibrosis is a common process that leads to the progression of various types of kidney disease. We used an integrated computational and experimental systems biology approach to identify protein kinases that regulate gene expression changes in the kidneys of human immunodeficiency virus (HIV) transgenic mice (Tg26 mice), which have both tubulointerstitial fibrosis and glomerulosclerosis. We identified homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of kidney fibrosis. HIPK2 was upregulated in the kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV infection increased the protein concentrations of HIPK2 by promoting oxidative stress, which inhibited the seven in absentia homolog 1 (SIAH1)-mediated proteasomal degradation of HIPK2. HIPK2 induced apoptosis and the expression of epithelial-to-mesenchymal transition markers in kidney epithelial cells by activating the p53, transforming growth factor β (TGF-β)-SMAD family member 3 (Smad3) and Wnt-Notch pathways. Knockout of HIPK2 improved renal function and attenuated proteinuria and kidney fibrosis in Tg26 mice, as well as in other murine models of kidney fibrosis. We therefore conclude that HIPK2 is a potential target for anti-fibrosis therapy.
    Nature medicine 03/2012; 18(4):580-8. DOI:10.1038/nm.2685 · 28.05 Impact Factor
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    ABSTRACT: To identify the correlation between serum-based differentially expressed proteins and pathological myopia. It was a case-control study. The serum of 30 pathological myopia patients and 30 age- and gender-matched normal controls were collected from Shanghai First People's Hospital affiliated to Shanghai Jiaotong University. These patients were divided into 4 groups including macular-off retinal detachment (8 cases), retinal geographic atrophy (5 cases), macular hole (11 cases) and choroidal neovascular (6 cases). The serum specimens of normal controls were used as immunogen to immune rabbits in order to prepare polyclonal antibodies. Purified by Protein A cartridge, these mixed antibodies were then combined with CNBr-activated Sepharose so as to synthesize affinity medium which was finally used to treat the serum specimens. According to the theory of antigen and antibody, common background proteins would be deleted. The remaining non-binding proteins were analyzed by capillary high-performance liquid chromatography and LTQ-MASS. Nonparametric statistical analysis was used to detect the correlation each differentially expressed protein. The result of HPLC and LTQ-MASS in 30 specimens of patients revealed 4 peaks of differentially expressed proteins including JTR (positive in 18 specimens, 60%), HP( positive in 11 specimens, 36.7%), HPX (positive in 10 specimens, 33.3%), APO (positive in 8 specimens, 26.7%). There were positive correlations between these 4 proteins (the correlation between TTR and HP, HPX, APO is r = 0.480, 0.577, 0.492; the correlation between HP and TTR, HPX, APO is r = 0.480, 0.783, 0.636; the correlation between HPX and TTR, HP, APO is r = 0.577, 0.783, 0.853; the correlation between APO and TTR, HP, HPX is r = 0.492, 0.636, 0.853; P < 0.05). In group of macular hole, TTR was positive expressed in 7 specimens while other differential proteins were low expression. In group of choroidal neovascular, TTR and HP were positive expressed in 6 specimens while HPX was significantly high in 5 specimens. In other two groups, the expression of 4 differential proteins was rather low. Screening molecular biomarkers by serum-based proteomics can efficiently exclude common proteins and find differential proteins correlated with pathological myopia. These differential proteins may become molecular biomarks of pathological myopia in the future.
    [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 03/2012; 48(3):246-52.
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    ABSTRACT: Recent studies have revealed that melatonin exerts strong anti-apoptotic effects. Retina secretes melatonin, and melatonin receptors are distributed in almost all the layers of retina, including the layer of retinal pigment epithelial (RPE) cells. However, it is not known whether melatonin inhibits apoptosis through its anti-oxidant effects and how it works in RPE cells. Here, we show that melatonin decreases H2O2-induced apoptosis in RPE cells partially through protection of mitochondria. Melatonin decreased reactive oxygen species in mitochondria and mitochondrial DNA damage, alleviated structural damage and inhibited cytochrome C release.
    Frontiers in Bioscience 01/2012; 17:1461-8. · 4.25 Impact Factor
  • Jun Shao, Yu Xin, Rongxiu Li, Ying Fan
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    ABSTRACT: To detect serum and vitreous transthyretin (TTR) in high myopia patients and to evaluate potential associations between TTR and clinical parameters and ocular pathologies, including different ocular pathologies. Serum samples from 16 high myopia patients and 4 controls were analyzed by LTQ-MASS. Serum samples from 116 high myopia patients and 86 healthy controls were tested by Western blots and ELISA. Eight healthy and 40 pathologic vitreous samples were analyzed by ELISA. And corresponding serum samples were also analyzed by ELISA. Significant increased TTR serum levels were detected in high myopia patients compared to healthy controls. The high levels of serum TTR were associated with ocular pathologies, long axial length, and low visual acuity. TTR in high myopia patients with macular hole and macular detachment was upregulated in both vitreous and the corresponding serum samples. TTR levels in serum samples of high myopia patients with long axial lengths were higher than in the vitreous. Serum TTR may be a biomarker for high myopia patients with ocular pathologies.
    Clinical biochemistry 03/2011; 44(8-9):681-5. DOI:10.1016/j.clinbiochem.2011.03.032 · 2.23 Impact Factor
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    ABSTRACT: to analyze the efficacy of low-energy selective laser trabeculoplasty (SLT) in patients. in 74 patients (74 eyes) with ocular hypertension, suspected glaucoma, or primary open-angle glaucoma, SLT was the first-choice treatment. Thirty-nine patients in the low-energy group received treatment using half of conventional laser energy over 360° of the trabecular meshwork (at 100 points). Thirty-five patients in the control group received conventional laser energy. Patients were observed for 1 year. Complications and intraocular pressure (IOP) were observed. postoperative transient IOP spike (≥ 3 mm Hg) occurred in three eyes on the day of treatment and partial peripheral anterior synechiae occurred in one eye 1 month after treatment only in the control group. Effective rates of treatment (≥ 20% IOP reduction) at week 2 and month 1, 3, 6, and 12 after treatment were 69.23%, 64.10%, 61.54%, 53.85%, and 48.72% in the low-energy group and 71.43%, 71.43%, 60%, 51.43%, and 48.57% in the control group, respectively. There was no statistically significant difference between the two groups at various time points (P = .836, .501, .892, .835, .990). compared with SLT using conventional laser energy, low-energy SLT lowers IOP with fewer complications, making it a safe and effective option.
    Ophthalmic Surgery Lasers and Imaging 01/2011; 42(1):59-63. DOI:10.3928/15428877-20101124-07 · 1.32 Impact Factor
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    ABSTRACT: To explore the value of color Doppler ultrasound in evaluating the therapeutic effects on ankylosing spondylitis (AS) patients. Color Doppler high-frequency ultrasound images and blood flow in 30 healthy volunteers and 50 AS patients, changes of high-frequency ultrasound images and blood flow of involved sites in AS patients pre- and after-Etanercept treatments, as well as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity indices pre- and post-treatment were compared. Positive rates were significantly different between healthy volunteers and AS patients in terms of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments, and rectus femoris tendon attachments by ultrasonograph (P < 0.05); and the fibular collateral ligament attachments positive rates had no significant difference with those at pre-treatment (P > 0.05). There was significant difference between patients with Bath AS disease activity index (BASDAI) ≥ 4 and those with BASDAI < 4 with respects to peripheral enthesis positive rate, Bath AS functional index (BASFI), patient's global assessment VAS (PGA), nocturnal back pain and general back pain VAS, morning stiffness duration, ESR and CRP (P < 0.05). Positive rates of sacroiliac joints, Achilles tendon attachments, patellar ligament attachments and rectus femoris tendon by ultrasonograph significantly decreased at Weeks 12 and 24 at post-treatment compared to that at pre-treatment (P < 0.05); there was significant difference for patient's BASDAI, BASFI, ESR and CRP at pre-treatment and weeks 12 and 24 post-treatment (P < 0.05). Ultrasound can sensitively detect the pathological changes of joint synovium and entheses so that it may be used as a routine method of monitoring diseases in these soft tissues, following up AS patients and evaluating clinical efficacy.
    Zhonghua yi xue za zhi 07/2010; 90(27):1897-901.
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    ABSTRACT: This study was designed to investigate whether synthetic small interference RNA (siRNA) targeting VEGF-A could inhibit mouse corneal neovascularization or not. First, the effect of synthetic siRNA targeting VEGF-A on the expression of VEGF in human retinal pigment epithelial line ARPE-19 cells was examined. Corneal neovascularization was induced on the right cornea of C57BL/6 mice by alkali burn. Mice were randomly divided into 4 groups (21 animals in each group): VEGF-A siRNA group, stable negative siRNA group, saline control group, and blank control group. After alkali burn, except for the blank control group, the other 3 groups were subconjunctivally injected with VEGF-A siRNA, stable negative siRNA, and normal saline, respectively. On days 3 and 7 after alkali burn, the concentration of VEGF in the cornea was determined by ELISA kit. On day 10, the neovascularized corneal area was mensurated, the amount of corneal new vessels was quantified by CD31 immunohistochemical assay of corneal sections, and permeability of new vessels was shown by fluorescence angiography. After comparing the histological appearance of the cornea between the VGF-A siRNA group and the 3 control groups on days 10 and 30, it was found that in the VEGF-A siRNA group, not only was VEGF expression in the cornea induced by alkali burn but also neovascularized corneal area and amount of new vessels were reduced, followed by the permeability of new vessels, and corneal histological structure were improved. It was also found that the exposure to VEGF-A siRNA significantly reduced the VEGF-A mRNA expression in AREP-19 cells. These findings suggested synthetic siRNA targeting VEGF-A delivered by subconjunctival injection could inhibit corneal angiogenesis induced by alkali burn. VEGF-A siRNA could potentially serve as an important therapeutic alternative in the management against unwanted angiogenesis including corneal neovascularization.
    Current eye research 05/2010; 35(5):375-84. DOI:10.3109/02713681003597230 · 1.66 Impact Factor
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    ABSTRACT: This study aimed to verify whether the decreased vascular endothelial growth factor (VEGF)-to-pigment epithelium-derived factor (PEDF) ratio can serve as an indicator for the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) on diabetic retinopathy (DR) and to investigate the role of mitochondrial reactive oxygen species (ROS) in the downregulated VEGF-to-PEDF ratio. Diabetic rats and control animals were randomly assigned to receive perindopril or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without perindopril. VEGF, PEDF, PPARgamma, and uncoupling protein-2 (UCP-2) in the rat retinas or BREC extracts were examined by Western blotting and real-time RT-PCR. The levels of VEGF and PEDF in cell culture media were examined by ELISA. Mitochondrial membrane potential (Deltapsim) and ROS production were assayed using JC-1 or CM-H2DCFDA. The VEGF-to-PEDF ratio was increased in the retina of diabetic rats; perindopril lowered the increased VEGF-to-PEDF ratio in diabetic rats and ameliorated the retinal damage. In BRECs, perindopril lowered the hyperglycemia-induced elevation of VEGF-to-PEDF ratio by reducing mitochondrial ROS. We found the decreased ROS production was a result of perindopril-induced upregulation of PPARgamma and UCP-2 expression and the subsequent decrease of Deltapsim. It is concluded that the protective effect of ACEI on DR is associated with a decreased VEGF-to-PEDF ratio, which involves the mitochondria-ROS pathway through PPARgamma-mediated changes of UCP-2. This study paves a way for future application of ACEI in treatment of DR.
    Diabetes 03/2009; 58(4):954-64. DOI:10.2337/db07-1524 · 8.47 Impact Factor
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    ABSTRACT: Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent.
    Biochemical and Biophysical Research Communications 06/2008; 369(2):718-24. DOI:10.1016/j.bbrc.2008.02.100 · 2.28 Impact Factor
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    ABSTRACT: Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization. Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays. Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However, the concentration of PEDF which we used has little effect on normal CECs. PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell. These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.
    Chinese medical journal 10/2007; 120(17):1534-8. · 1.02 Impact Factor
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    ABSTRACT: CD146 is a cell adhesion molecule belonging to the immunoglobulin superfamily. It plays a critical role in cell proliferation and activation, and contributes to inflammatory reactions. We studied the association between CD146 and renal tubular epithelial cells (RTECs) under normal (NG) and high glucose (HG) to understand its role in the pathogenesis of diabetic nephropathy. Human proximal tubular epithelial (HK-2) cells were cultured in different glucose media (NG5mM, HG15mM and HG40mM). CD146 mRNA expression was determined by RT-PCR. CD146 protein expression was assessed by fluorescence immunoassay, enzymatic immunohistochemistry and flow cytometry. A soluble form of CD146 was evaluated by ELISA. We found weak expression of CD146 mRNA and protein in the NG group. Faint labeling of CD146 protein was detected mainly at the cell-cell junction, with sparse staining in cytoplasm and nucleus. In the HG group, both membrane and intracellular expression of CD146 were significantly increased by high glucose, while osmotic pressure had no effect on CD146 expression in cultured HK-2 cells. A soluble form of CD146, sCD146, was detected in the supernatant of HK-2 cells in the NG group which was elevated in the HG40mM group (29.33 -/+ 1.22 ng/mL vs. 61.87 -/+ 9.10 ng/mL, p<0.05). CD146 might be a novel marker for RTECs, correlating with cell proliferation and cell-cell conjunctions. High glucose up-regulates both CD146 and sCD146 expression. CD146 may be a biomarker of activated RTECs, and sCD146 may have clinical value for determining severity and prognosis of diabetic nephropathy.
    Journal of nephrology 21(6):931-40. · 2.00 Impact Factor

Publication Stats

157 Citations
72.17 Total Impact Points

Institutions

  • 2012–2015
    • Icahn School of Medicine at Mount Sinai
      • Department of Medicine
      Borough of Manhattan, New York, United States
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2008–2014
    • Shanghai Jiao Tong University
      • Department of Ophthalmology
      Shanghai, Shanghai Shi, China
  • 2009–2010
    • Shanghai University
      • Department of Ophthalmology
      Shanghai, Shanghai Shi, China