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ABSTRACT: Glomerulonephritis is one of the most important causes of renal failure, which is accompanied with production of Nitric Oxide (NO) synthesized by inducible nitric oxide synthase (iNOS). Aldose reductase (AR) is the key enzyme in polyol pathway and plays an important role in glucose metabolism. Here, we report our finding that AR regulates tumor-necrosis-factor-α-induced (TNF-α-induced) iNOS expression in human mesangial cells (HMC) via nuclear factor κB (NFκB) signal pathway. The TNF-α-induced iNOS expression in HMC with different level of AR was measured by Real-time PCR and Western blot. The activation of signal pathway was analyzed by Western blot and electrophoretic mobility shift assay (EMSA). In cultured HMC, TNF-α induces the expression of iNOS, which is attenuated by knockdown AR with siRNA. On the other side, transfection with pcDNA3.1-AR gets the consistent conclusion. Furthermore, knockdown of AR attenuated activity of NFκB, suggesting that the effects of AR on this pathway may result in the reduced iNOS transcription and expression. Taken together, these data demonstrate the role of AR in regulating iNOS expression induced by TNF-α in cultured HMC, indicating the novel function of AR in glomerulonephritis besides glucose metabolism.
Molecular Biology Reports 06/2011; 39(2):1815-22. · 2.93 Impact Factor
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ABSTRACT: This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Experimental and Molecular Pathology 08/2010; · 2.42 Impact Factor
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ABSTRACT: Aldose reductase (AR) has emerged as a key contributor to the diabetic nephropathy (DN), however, the mechanisms by which AR increases DN remain poorly understood. Here, we report that exposure to high glucose (HG) stimulates fibronectin (FN) from human mesangial cells in culture. Our results show that exposure to HG and overexpression AR increase the expression of FN. This increase was prevented by the AR inhibitors sorbinil and zopolrestat. Treatment with HG and transfected with plasmid PcDNA3.0-AR, resulted in phosphorylation and activation of ERK, JNK and AKT signaling pathway, and increase the expression of FN. Treatment with inhibitor of JNK and AKT signaling pathway decreased the expression of FN. These results show that inhibition of AR may be useful to prevented extracellular matrix (ECM) deposition in diabetic nephropathy, which is regulated by JNK and AKT.
Molecular Biology Reports 10/2009; 37(6):3017-21. · 2.93 Impact Factor
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ABSTRACT: Accumulation of glomerular extracellular matrix (ECM) may result in glomerulosclerosis. Several lines of evidence indicate a key role for transforming growth factor-beta1 (TGF-beta1) in glomerular ECM synthesis and degradation, such as fibronectin (FN). Aldose reductase (AR) was proven to be one of the TGF-beta1 responsive genes in cultured rat mesangial cells using the SSH-PCR method and there were positive correlation between the AR and TGF-beta1 in our previous studies. So we assumed that AR could regulate FN synthesis. In this study, we explored the role of AR in FN production and possible mechanism involved. The expression of AR, FN and c-Jun proteins were analyzed by Western blot and the activity of activator protein-1 (AP-1) was assessed by electrophoretic mobility shift assay (EMSA). Our results showed that AR could mediate the TGF-beta1-induced FN production, which may associate with AP-1 activation.
Molecular Biology Reports 09/2009; 37(6):2735-42. · 2.93 Impact Factor
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Yongqing Li, Yuejuan Zhang,
Bei He,
Yuequn Wang,
Zengjin Yuan,
Wuzhou Yuan,
Peng Liao,
Yun Deng,
Jing Xiao,
Chuanbing Zhu,
Ying Wang,
Xiushan Wu,
Mingyao Liu
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ABSTRACT: The LIM-homeodomain (LIM-HD) proteins have a homeodomain and two N-terminal LIM domains, which consist of a conserved cysteine- and histidine-rich structure of two tandem repeated zinc fingers. LIM domain is involved in protein-protein interactions during transcriptional regulation. LIM-HD proteins are classically suggested as major transcriptional regulators which, in cooperation with other transcription factors, play critical roles in several developing systems and organs, such as nervous system, pancreas, and heart. Here we have cloned the full-length cDNA of human Isl-2 from a human embryo heart cDNA library. The gene contains six exons and spans 5.7 kb in chromosome 15q23 region, and transcribes a 1.9 kb mRNA that encodes a protein with 359 amino acid residues. The predicted protein, containing two tandem LIM motifs in N-terminal and a homeodomain domain, is well conserved, especially in the LIM and DNA-binding domains. Northern blot analysis shows that human Isl-2 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 34 days to 24 weeks at different levels in tissues. The broad expression of Isl-2 gene in tissues during embryogenesis and adult development suggests that it may be involved in both differentiation and maintenance of these tissues and might play an important role.
Molecular Biology Reports 04/2007; 34(1):19-26. · 2.93 Impact Factor
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Chunxia Huang,
Yuequn Wang,
Dali Li,
Yongqing Li,
Jian Luo,
Wuzhou Yuan,
Ying Ou,
Chuanbing Zhu, Yuejuan Zhang,
Zhi Wang,
Mingyao Liu,
Xiushan Wu
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ABSTRACT: Zinc finger proteins play important roles in a variety of cellular functions, including cell growth, proliferation, apoptosis, and intracellular signal transduction, and the zinc finger-containing transcription factor has been implicated as a critical regulator of multiple cardiac-expressed genes as well as a regulator of inducible gene expression in response to hypertrophic stimulation. With the aim of identifying the genes involved in human heart development and diseases, we have isolated a novel LER-related zinc finger gene named ZNF394 from human heart cDNA library. ZNF394 gene has a predicted 561-amino acid open reading frame, encoding a 64kDa zinc finger protein. The N-terminus of ZNF394 protein has a leucine-rich region (LER or SCAN domain), followed by a well-conserved krüppel-associated box domain. The C-terminus of the protein contains 7 C2H2 zinc finger motifs in tandem arrays with the highly conserved space region of the H/C-link. ZNF394 gene is mapped to chromosome 7q11.21. Northern blot analysis indicates that a 2.18kb transcript specific for ZNF394 is specifically expressed in the heart, skeletal muscle, and brain in human adult tissues. ZNF394 protein is expressed in cell nucleus. Overexpression of ZNF394 in the cell inhibits the transcriptional activities of c-Jun and AP-1 reporters, suggesting that ZNF394 is a new transcriptional repressor in mitogen-activated protein kinase signaling pathways and may play an important role in cardiac development and/or cardiac function.
Biochemical and Biophysical Research Communications 09/2004; 320(4):1298-305. · 2.48 Impact Factor
