Shengdong Huang

Changhai Hospital, Shanghai, Shanghai, Shanghai Shi, China

Are you Shengdong Huang?

Claim your profile

Publications (33)85.6 Total impact

  • Source
    Ming Chen · Bing Yi · Ni Zhu · Xin Wei · Guan-Xin Zhang · Shengdong Huang · Jianxin Sun
    [Show abstract] [Hide abstract] ABSTRACT: Aims: Posttranslational modification, such as phosphorylation, plays an essential role in regulating activation of endothelial NO synthase (eNOS). In the present study, we aim to determine whether eNOS could be phosphorylated and regulated by a novel serine/threonine-protein kinase Pim1 in vascular endothelial cells (ECs). Methods and results: Using immunoprecipitation and protein kinase assays, we demonstrated that Pim1 specifically interacts with eNOS, which leads to a marked phosphorylation of eNOS at Ser-633 and increased production of nitric oxide (NO). Intriguingly, in response to VEGF stimulation, eNOS phosphorylation at Ser-633 exhibits two distinct phases: transient phosphorylation occurring between 0 and 60 min and sustained phosphorylation occurring between 2 and 24 h, which are mediated by the protein kinase A (PKA) and Pim1, respectively. Inhibiting Pim1 by either pharmacological inhibitor SMI-4a or the dominant negative form of Pim1 markedly attenuates VEGF-induced tube formation, while Pim1 overexpression significantly increases EC tube formation and migration in a NO dependent manner. Importantly, Pim1 expression and eNOS phosphorylation at Ser-633 were substantially decreased in high glucose treated-ECs and in the aorta of db/db diabetic mice. Increased Pim1 expression ameliorates impaired vascular angiogenesis in diabetic mice, as determined by an ex vivo aortic ring assay. Conclusion: Our findings demonstrate Pim1 as a novel kinase that is responsible for the phosphorylation of eNOS at Ser-633 and enhances endothelial cell sprouting of aortic rings from diabetic mice, suggesting that Pim1 could potentially serve as a novel therapeutic target for revascularization strategies.
    Full-text · Article · Nov 2015 · Cardiovascular Research
  • Bing Yi · Maria Ozerova · Guan-Xin Zhang · Guijun Yan · Shengdong Huang · Jianxin Sun
    [Show abstract] [Hide abstract] ABSTRACT: Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular function and its expression is regulated at post-transcriptional levels through a yet unknown mechanism. The purpose of this study is to elucidate the post-transcriptional factors regulating eNOS expression and function in endothelium. To elucidate the molecular basis of tumor necrosis factor (TNF)-α-mediated eNOS mRNA instability, biotinylated eNOS 3'-untranslational region (UTR) was used to purify its associated proteins by RNA affinity chromatography from cytosolic fractions of TNF-α-stimulated human umbilical vein endothelial cells (HUVECs). We identified 2 cytosolic proteins, with molecular weight of 52 and 57 kDa, which specifically bind to eNOS 3'-UTR in response to TNF-α stimulation. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis identified the 57-kDa protein as polypyrimidine tract-binding protein 1 (PTB1). RNA gel mobility shift and UV cross-linking assays demonstrated that PTB1 binds to a UCUU-rich sequence in eNOS 3'-UTR, and the C-terminal half of PTB1 is critical to this interaction. Importantly, PTB1 overexpression leads to decreased activity of luciferase gene fused with eNOS 3'-UTR as well as reduced eNOS expression and activity in human ECs. In HUVECs, we show that TNF-α markedly increased PTB1 expression, whereas adenovirus-mediated PTB1 overexpression decreased eNOS mRNA stability and reduced protein expression and endothelium-dependent relaxation. Furthermore, knockdown of PTB1 substantially attenuated TNF-α-induced destabilization of eNOS transcript and downregulation of eNOS expression. These results indicate that PTB1 is essential for regulating eNOS expression at post-transcriptional levels and suggest a novel therapeutic target for treatment of vascular diseases associated with inflammatory endothelial dysfunction. © 2015 American Heart Association, Inc.
    No preview · Article · Aug 2015 · Arteriosclerosis Thrombosis and Vascular Biology
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases and its expression is markedly induced in the heart after β-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using northern blot, western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly up-regulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and Endothelin-1 (ET-1). In a time and dose dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation of Nur77 in cardiomyocytes. Furthermore, cardiac overexpression of Nur77 by intramyocardial injection of Ad-Nur77 substantially inhibited cardiac hypertrophy and ameliorated cardiac dysfunction after chronic infusion of ISO in mice. Mechanistically, we demonstrated that Nur77 functionally interacts with NFATc3 and GATA4, and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy. These results demonstrate for the first time that Nur77 is a novel negative regulator for the β-AR induced cardiac hypertrophy through inhibiting the NFATc3 and GATA4 transcriptional pathways. Targeting Nur77 may represent a potentially novel therapeutic strategy for preventing cardiac hypertrophy and heart failure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jul 2015 · Molecular and Cellular Biology
  • Source
    Yang Yuan · Weixing Wang · Huizhong Li · Yongwei Yu · Jin Tao · Shengdong Huang · Zhiyong Zeng
    [Show abstract] [Hide abstract] ABSTRACT: Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS.
    Preview · Article · May 2015 · BMC Cancer
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Androgen receptor (AR) is a ligand dependent transcription factor that regulates the transcription of target genes. AR activity is closely involved in the maintenance and progression of prostate cancer. After the binding with androgen, AR moves into nucleus and binds to DNA sequence containing androgen response elements (ARE). Flavin-dependent monoamine oxidase KDM1A is necessary for AR driven transcription while the mechanism remains unclear. The association between androgen-dependent transcription and oxidation was tested through pharmaceutical inhibitions and siRNA knockdown of DNA oxidation repair components in prostate cancer cells. The recruitment of involved proteins and the histone methylation dynamics on ARE region was explored by chromatin immunoprecipitation (ChIP). Oxidation inhibition reduced AR dependent expression of KLK3, TMPRSS2, hsa-miR-125b2, and hsa-miR-133b. And such reduction could be restored by H2 O2 treatment. KDM1A recruitment and H3K4me2 demethylation on ARE regions, which produce H2 O2 , are associated with AR targets transcription. AR targets transcription and coupled oxidation recruit 8-oxoguanine-DNA glycosylase (OGG1) and the nuclease APEX1 to ARE regions. Such recruitment depends on KDM1A, and is necessary for AR targets transcription. Our work underlined the importance of histone demethylation and DNA oxidation/repairing machinery in androgen-dependent transcription. The present finds have implications for research into new druggable targets for prostate cancer relying on the cascade of AR activity regulation. Prostate © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · The Prostate
  • Source
    Yang Yuan · Chong Wang · Jibin Xu · Jin Tao · Zhiyun Xu · Shengdong Huang
    [Show abstract] [Hide abstract] ABSTRACT: Background: Here we investigated Brahma-related gene 1 (BRG1) expression in aortic smooth muscle cells (SMCs) and its role in the regulation of the pathological changes in aortic SMCs of thoracic arotic dissection (TAD). Methods: BRG1, matrix metalloproteinase 2 (MMP2), and MMP9 mRNA and protein expression in human aortic specimens were examined by qPCR and western blot, respectively. The percentage of apoptotic and contractile SMCs in aortic specimens were determined by TUNEL assay and alpha-SMA immunohistochemical staining, respectively. The role of BRG1 in MMP2 and MMP9 expression, cell apoptosis, and phenotype transition in aortic SMCs were investigated using a human aortic SMC line via adenovirus mediated gene transfer. MMPs mRNA and protein levels were analyzed by qPCR and western blot, respectively. The percentage of apoptotic and contractile cells were determined through flow cytometry analysis. Results: The expression level of BRG1 in the aortic walls (adventitia-removed) was significantly higher in the TAD than the normal group. BRG1 expression was positively correlated to expression of MMP2 and MMP9 and SMC apoptosis, but was negatively correlated to the percentage of contractile aortic SMCs in TAD specimens. In human aortic SMC line, BRG1 transfection led to significant upregulation of MMP2 and MMP9 expression and a concomitant increase in SMC apoptosis as well as a decrease in the percentage of contractile phenotype of cells. Conclusions: BRG1 is significantly upregulated in the aortic SMCs of TAD, and its overexpression might promote the development of TAD by increasing MMP2 and MMP9 expression, inducing SMC apoptosis and the transition from contractile to synthetic phenotype.
    Preview · Article · Oct 2014 · BMC Cardiovascular Disorders
  • Guijun Yan · Qing Qin · Bing Yi · Kurt Chuprun · Haixiang Sun · Shengdong Huang · Jianxin Sun
    [Show abstract] [Hide abstract] ABSTRACT: Background: Mammalian sterile 20-like kinase 1 (Mst1) is a mammalian homolog of Hippo kinase from Drosophila and it is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression in mammals. Mst1 plays essential roles in heart disease since its activation causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart is not known. Methods and results: To identify novel cardiac proteins that may regulate Mst1 activity in the heart under pathophysiological conditions, a yeast two-hybrid screening of a human heart cDNA library with a dominant-negative Mst1 (K59R) mutant used as bait was performed. As a result, protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) was identified as an Mst1-interacting protein. The interaction of PCMT1 with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK293 cells and native cardiomyocytes, in which PCMT1 interacted with the kinase domain of Mst1, but not with its C-terminal regulatory domain. Overexpression of PCMT1 did not affect the Mst1 expression, but significantly attenuated the Mst1 activation and its apoptotic effects in response to the hypoxia/reoxygenation induced injury in cardiomyocytes. Indeed, upregulation of PCMT1 by CGP3466B, a compound related to the anti-Parkinson's drug R-(-)-deprenyl with potent antiapoptotic effects, inhibited the hypoxia/reoxygenation induced Mst1 activation and cardiomyocyte apoptosis. Conclusions: These findings implicate PCMT1 as a novel inhibitor of Mst1 activation in cardiomyocytes and suggest that targeting PCMT1 may prevent myocardial apoptosis through inhibition of Mst1.
    No preview · Article · May 2013 · International journal of cardiology
  • Source
    Bei You · Shengdong Huang · Qing Qin · Bing Yi · Yang Yuan · Zhiyun Xu · Jianxin Sun
    [Show abstract] [Hide abstract] ABSTRACT: Mammalian sterile 20-like kinase 1 (Mst1) is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression in mammals. Mst1 plays essential roles in the heart disease since its activation causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart remains unknown. In a yeast two-hybrid screen of a human heart cDNA library with Mst1 as bait, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as an Mst1-interacting protein. The interaction of GAPDH with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK293 cells and mouse heart homogenates, in which GAPDH interacted with the kinase domain of Mst1, whereas the C-terminal catalytic domain of GAPDH mediated its interaction with Mst1. Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells. Chelerythrine, a potent inducer of apoptosis, substantially increased the nuclear translocation and interaction of GAPDH and Mst1 in cardiomyocytes. Overexpression of GAPDH significantly augmented the Mst1 mediated apoptosis, whereas knockdown of GAPDH markedly attenuated the Mst1 activation and cardiomyocyte apoptosis in response to either chelerythrine or hypoxia/reoxygenation. These findings reveal a novel function of GAPDH in Mst1 activation and cardiomyocyte apoptosis and suggest that disruption of GAPDH interaction with Mst1 may prevent apoptosis related heart diseases such as heart failure and ischemic heart disease.
    Preview · Article · Mar 2013 · PLoS ONE
  • Source
    Dataset: Table S2
    [Show abstract] [Hide abstract] ABSTRACT: Pairwise polymorphisms LD analysis. (DOC)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Figure S1
    [Show abstract] [Hide abstract] ABSTRACT: The flow chart of the included studies. (TIFF)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Table S3
    [Show abstract] [Hide abstract] ABSTRACT: Meta analysis of haplotype combinations between −429T/C, −374T/A, and G82S polymorphisms of RAGE gene and CHD risk. (DOC)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Figure S3
    [Show abstract] [Hide abstract] ABSTRACT: Begg’s funnel plot of RAGE −429T/C polymorphism and coronary heart disease risk. (TIFF)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Table S1
    [Show abstract] [Hide abstract] ABSTRACT: Minor allele distribution in cases and controls. (DOC)
    Preview · Dataset · Dec 2012
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: PRISMA Checklist. (DOC)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Figure S2
    [Show abstract] [Hide abstract] ABSTRACT: Begg’s funnel plot of RAGE −374T/A polymorphism and coronary heart disease risk. (TIFF)
    Preview · Dataset · Dec 2012
  • Source
    Dataset: Figure S4
    [Show abstract] [Hide abstract] ABSTRACT: Begg’s funnel plot of RAGE G82S polymorphism and coronary heart disease risk. (TIFF)
    Preview · Dataset · Dec 2012
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Recent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product-specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (-429T/C, -374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results. PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. A total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for -429T/C (OR  = 1.01, 95% CI: 0.92-1.12, P  = 0.78), -374T/A (OR  = 1.11, 95% CI: 0.98-1.26, P  = 0.09) and G82S (OR  = 1.12, 95% CI: 0.86-1.45, P  = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained. This meta-analysis demonstrates that there is no association between the RAGE -429T/C, -374T/A and G82S polymorphisms and CHD.
    Preview · Article · Dec 2012 · PLoS ONE
  • Xiaohong Liu · Mengwei Tan · Dejun Gong · Lin Han · Fanglin Lu · Shengdong Huang · Zhiyun Xu
    [Show abstract] [Hide abstract] ABSTRACT: Pericardial fibrocalcification (PF) is a prominent feature of human pericardial pathology, including constrictive pericarditis and, to a lesser extent, degenerated autologous pericardial substitutes. However, the role of pericardial interstitial cells (PICs) in the pathogenesis of PF has yet to be established. Using a combination of histology and immunohistochemistry, we showed that the critical cellular event in PF in situ was the transdifferentiation of PICs into myofibroblasts/osteoblasts and that the percentage of myofibroblasts/osteoblasts correlated positively with the severity of PF. In vitro studies demonstrated that PICs, similar to mesenchymal stem cells, had the potential to differentiate along adipogenic, osteogenic, chondrogenic or myogenic lineages. However, PICs exhibited a more limited self-renewal capacity and a lower expression of Oct4 (POU5F1) and Kruppel-like transcription factor Klf4, underwent earlier senescence and spontaneously transdifferentiated into myofibroblasts/osteoblasts. Quantitative-real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) confirmed that the mRNA levels of α-smooth muscle actin (α-SMA), alkaline phosphatase (ALP), core-binding factor α1/runt-related transcription factor2 (Cbfa1/Runx2), transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 were upregulated as the passage number increased. The mRNA level of platelet-derived growth factor (PDGF)-AA was also significantly upregulated with higher levels at passage 3. Ectopic expression of Oct4 and Klf4 enhanced the colony formation of PICs and selectively impaired induction of genes involved in transdifferentiation into myofibroblasts/osteoblasts (α-SMA, ALP, Cbfa1/Runx2, PDGF-AA and BMP-2). These data, while offering new insights into the biology of PICs, reinforce the central role of these cells in cell-mediated PF and may assist in future strategies to treat fibrocalcific pericardial diseases.
    No preview · Article · Dec 2012 · Journal of Molecular and Cellular Cardiology
  • Bailing Li · Keng Zhong · Lei Jin · Yang Yuan · Dejun Gong · Xiaohong Liu · Shengdong Huang
    [Show abstract] [Hide abstract] ABSTRACT: Lung cancer is a major worldwide health problem. The aim of this study is to establish a novel Chinese human lung adenocarcinoma cell line and examine its biological characteristics. Lung adenocarcinoma specimens were freshly resected during surgery. The tissues were incubated in vitro and the cell line was named Ch-Huang-1. The biological characteristics of the cells were investigated by light microscopy, chromosome analysis, and transplantation experiment. Light microscopy revealed that cells from the primary tumor, Ch-Huang-1 cell line, and transplanted tumor possessed the characteristics of a malignant glandular epithelial tumor. The cell growth curve, doubling time, and mitotic index were also observed in vitro. Nuclear chromosome analysis revealed that the tumor was a subtriploid with a mode of 35-44 per cell. Tumor nodes were observed under the skin of nude mice by heterogenic transplantation. The characteristics of the established cell line suggest that it is a newly established human adenocarcinoma cell line.
    No preview · Article · May 2012 · Zhongguo fei ai za zhi = Chinese journal of lung cancer
  • [Show abstract] [Hide abstract] ABSTRACT: It is well-known that angiopoietin-2 (Ang-2) plays an important role in the formation of the blood vascular system. Angiopoietin is involved in many diseases about angiogenesis such as tumor, so may have great prospects for the treatment of these diseases. The aim of this study is to evaluate the influence of inhibiting Ang-2 via adeno-associated virus induced RNA interference (RNAi) on the biological characteristics of bronchogenic adenocarcinoma. AAV-Ang-2shRNA driven by H1 promoter was constructed to transfect A549 cell line. Normal and AAV-Null cell line were utilized in the control groups. The influence of RNAi on Ang-2 expression as well as the growth rate, tumorigenic efficiency, proliferation rate, apoptosis, and microvessel density of A549 cell line were analyzed. In vitro experiment indicated that the Ang-2 expression level (P<0.001) and growth rate (P<0.001) of A549 cell line 48 h transfected with AAV-Ang-2shRNA were significantly lower than those in the normal and AAV-Null cell lines. Cell cycle analysis showed the proliferation index (PI) of normal, AAV-Null, and AAV-Ang-2shRNA transfected A549 cell line were 0.51± 0.43, 0.48 ± 0.29, and 0.26 ± 0.31, respectively, which indicated the PI of AAV-Ang-2shRNA transfected cell line was significantly lower, compared with the normal and AAV-Null cell lines. In vivo experiment exhibited that AAV-Ang-2shRNA transfected cell line possessed a lower mass and volume of tumor relative to two control groups. In addition, the apoptosis index (AI) of AAV-Ang-2shRNA transfected, normal, and AAV-Null cell lines were (5.98 ± 3.11)%, (7.51 ± 4.42)% and (17.06 ± 7.43)% respectively, which manifested that AAV-Ang-2shRNA transfected cell line possessed a higher AI (P=0.005, P=0.007). A lower percentage of PCNA-positive cell was observed in AAV-Ang-2shRNA transfected cell line (92.75 ± 9.7)% as well, compared with the normal (85.8 ± 11.8)% and AAV-Null (69.8 ± 16.5)% cell lines. AAV-mediated expression of shRNA significantly reduces concentration of Ang-2 in A549 cell line, lowers proliferation and growth rate and induce .apoptosis of A549 cell line.
    No preview · Article · Jul 2011 · Zhongguo fei ai za zhi = Chinese journal of lung cancer