Biomedical subjects

Jianzhong Wang

Publications and source records attributed to Jianzhong Wang.

15 recordsLinked to original sources

PubMed2025

EucaMOD: a comprehensive multi-omics database for functional genomics research and molecular breeding of fast-growing eucalyptus trees.

Eucalyptus, one of the most widely planted plantation tree species globally, is primarily found in tropical and subtropical regions and contributes significantly to economic and social benefits. With advances in sequencing technologies, there is an increasing demand for the systematic analysis of multi-omics data among Eucalyptus species to enhance genetic breeding efforts. Although several early genomic databases have been established for eucalyptus, they have not been updated in a timely manner and lack recent multi-omics data, rendering them insufficient for current research needs. To address this gap, we developed the eucalyptus multi-omics database (EucaMOD, http://eucalyptusggd.net/eucamod), a comprehensive resource for cross-omics studies. In this study, we functionally annotated 45 eucalyptus genomes and structurally annotated 15, conducting comparative genomics and pan-proteomics analyses across all genomes. Additionally, we analyzed eucalyptus transcriptome, epigenome, and variome data through standardized workflows, enabling the in-depth mining and reanalysis of multi-omics datasets. EucaMOD is the most comprehensive multi-omics database for eucalyptus to date and includes data from 45 genomes (39 species), 870 mRNA-seq samples, 17 miRNA-seq samples, 52 epigenomic datasets (histone modifications and transcription factor binding), and genetic variation data from 1219 samples. To support functional genomics and molecular breeding research, the database is organized into the following 11 modules: Home, Species, Genomics, Comparative genomics, Pan-proteomics, Transcriptomics, Epigenetics, Variomics, Tools, Download, and Help. EucaMOD also offers online analysis tools for data mining, providing free public services to aid eucalyptus gene function and genetic engineering studies.

Eucalyptus↗

PubMed2007

TIMP-1 transgenic mice recover from diabetes induced by multiple low-dose streptozotocin.

Type 1 diabetes results from autoimmune destruction of the insulin-producing beta-cells of pancreatic islets, of which the capacity for self-replication in the adult is too limited to restore following extensive tissue injury. Tissue inhibitor of metalloproteinase (TIMP)-1 inhibits matrix metalloproteinase activity and regulates proliferation and apoptosis of a variety of cells types, depending on the context. Here, we show that overexpression of human TIMP-1 in pancreatic beta-cells of transgenic mice counteracts the cytotoxicity and insulitis induced by multiple low-dose streptozotocin (MLDS). Nontransgenic mice developed severe hyperglycemia, hypoinsulinemia, and insulitis 2 weeks after streptozotocin administration and died within 17 weeks. However, MLDS-treated transgenic mice gradually normalized the metabolic parameters and survived. beta-Cell mass increased in parallel as a result of enhancement of beta-cell replication. Thus, our results have demonstrated for the first time that overexpression of TIMP-1 in beta-cells enhances the replication of pancreatic islets beta-cells and counteracts type 1 diabetes, indicating that the TIMP-1 gene may be a potential target to prevent, or even reverse, type 1 diabetes.

Animals↗

PubMed2006

Development of high-specificity antibodies against renal urate transporters using genetic immunization.

Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1). Antibodies against these transporters are very important for investigating their expressions and functions. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages including high specificity and high recognition to the native protein compared with current methods. We fused high antigenicity fragments of the three transporters to the plasmids pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin, respectively. Gene gun immunization with these recombinant plasmids and two other adjuvant plasmids, which express granulocyte/ macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, induced high level immunoglobulin G antibodies, respectively. The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry. Besides, URAT1 expression in Xenopus oocytes can also be recognized by its corresponding antibody with immuno-fluorescence. The successful production of the antibodies has provided an important tool for the study of UA transporters.

Animals↗

PubMed2006

Downregulation of connexin 43 expression by high glucose induces senescence in glomerular mesangial cells.

Connexin 43 (Cx43) plays an important role in cell differentiation and growth control, but whether it can be regulated by high glucose and whether it can mediate in glomerular mesangial cells (GMC) the phenotype alterations that are induced by high glucose still remain to be explored. In this study, RNA interference and gene transfer techniques were used to knock down and overexpress Cx43 gene in rat GMC to determine the contribution of Cx43 to GMC senescence that was induced by high glucose. The results show that high glucose (30 mM) not only downregulated Cx43 mRNA and protein expression (P<0.05) but also increased the percentage of senescence-associated beta-galactosidase (SA-beta-gal) stained cells and expression of p21cip1 and p27kip1 (P<0.05), indicating that high glucose promoted rat GMC senescence. Knocking down Cx43 gene expression significantly increased the percentage of SA-beta-gal stained cells and p27kip1 and p21cip1 expression in GMC (P<0.05), whereas overexpression of Cx43 significantly decreased the percentage of SA-beta-gal stained cells (P<0.05). These results demonstrate for the first time that downregulation of Cx43 expression by high glucose promotes the senescence of GMC, which may be involved in the pathogenesis of diabetic nephropathy.

Animals↗

PubMed2006

TIMP-1 promotes age-related renal fibrosis through upregulating ICAM-1 in human TIMP-1 transgenic mice.

Imbalance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) takes part in age-related renal fibrosis; so does molecular inflammation. As several inflammatory mediators including intercellular adhesion molecule-1 (ICAM-1) are substrates of MMPs, we speculated that TIMP-1 might affect ICAM-1 through MMPs and subsequently promote age-related renal fibrosis. Then, we observed changes of kidney in human TIMP-1 transgenic mice and wild-type mice of different ages. It was found that the expressions and activities of gelatinases were downregulated; the expressions of ICAM-1, collagen III, collagen IV, and transforming growth factor (TGF)-beta1 were upregulated; and the number of infiltrating macrophages was increased in kidneys of 24-month-old TIMP-1 transgenic mice with high expressions of TIMP-1, compared with wild-type mice. Our results indicated that TIMP-1 could promote age-related renal fibrosis, which was partly attributed to enhancing inflammation through upregulation of ICAM-1.

Aging↗

PubMed2005

Expression and activation of STAT3 in chronic proliferative immune complex glomerulonephritis and the effect of fosinopril.

BACKGROUND: Signal transducers and activators of transcription (STATs) are cytoplasmic proteins that are activated in response to stimulation from various cytokines. Among these, STAT3 is an important member that has been implicated in the inflammatory proliferation of cells. We hypothesized that STAT3 may be activated in kidneys of rats having modified chronic immune complex glomerulonephritis, and that angiotensin-converting enzyme (ACE) inhibition with fosinopril may prevent the activation of STAT3 and subsequent upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1), which are effects that may explain the therapeutic effects of fosinopril on nephritis. METHODS: Fifty-one Wistar rats were randomly divided into three groups that included a control group, a model group and a fosinopril group. Bovine serum albumin (BSA) nephritis was induced by subcutaneous immunization and daily intraperitoneal (i.p.) administration of BSA. To accentuate the nephritis, we performed uni-nephrectomy and gave 100 microg of lipopolysaccharide (LPS) as an i.p. injection. Macrophage infiltration (ED-1) was assessed with immunohistochemistry. The expression and activation of STAT3 and the expression of TIMP-1, one of the STAT3 downstream genes, were observed in renal tissues of rats by means of immunohistochemistry, electrophoretic mobility shift assay (EMSA), western blot and northern blot. The relationships between STAT3 phosphorylation, 24 h urinary protein excretion and TIMP-1 expression were also analysed. RESULTS: Northern blot showed that the mRNA expression of both STAT3 and TIMP-1 was significantly increased in kidneys from the model group, but significantly decreased in the fosinopril group (P<0.05). Western blot analysis revealed similar increases in the expression of STAT3, phospho-STAT3 (p-STAT3) and TIMP-1 in the model group. Analysis of immunohistochemistry showed that STAT3 and p-STAT3 were expressed in very few cells of normal rats, that expression was strong in model rats and that this increased expression was attenuated in the fosinopril group (P<0.05). The expression of p-STAT3 in glomeruli was positively correlated with 24 h proteinuria as well as with glomerular TIMP-1 expression. Double staining showed that some ED-1-positive cells also contained p-STAT3-positive staining. CONCLUSIONS: The present study showed that STAT3 is expressed and activated in kidneys of rats with modified immune complex glomerulonephritis. These rats also had increased ED-1-positive cells, with some cells showing simultaneous expression of p-STAT3 and ED-1, which may contribute to glomerular inflammatory proliferation and extracellular matrix accumulation. Finally, fosinopril downregulated STAT3 activation and ED-1 influx, which are effects that may attenuate renal damage in this model.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Effects of human Na(+)/dicarboxylate cotransporter 3 on the replicative senescence of human embryonic lung diploid fibroblasts.

To investigate the role of human Na(+)/dicarboxylate cotransporter 3 (hNaDC3) in the replicative senescence of normal human embryonic lung diploid fibroblasts (WI-38), a retroviral vector containing hNaDC3 was constructed. hNaDC3 was introduced into normal WI-38 cells through infection with the retroviral virus. Monoclones were selected with G418. The integration and expression of exotic genes were confirmed by Northern blot and Western blot. When compared with the control cells, WI-38 cells transfected with hNaDC3 cDNA showed significant suppression of growth rate (by 40%), increase of positive rate of SA-beta-gal staining, decrease of mitochondrial membrane potential, shortening of telomere length, and increase of P16 and P21 expression. The morphology characteristics of senescent fibroblasts appeared earlier. Our results have, for the first time, demonstrated that high expression of hNaDC3 may be able to, at least partly, promote the cellular senescence of human diploid fibroblasts.

Blotting, Northern↗

PubMed2005

Mitochondrial pathway is responsible for aging-related increase of tubular cell apoptosis in renal ischemia/reperfusion injury.

Aging-related changes of tubular cell apoptosis and its mechanisms in renal ischemia/reperfusion (I/R) injury are unclear. In the present study, aged (27-month-old) and young (3-month-old) Wistar rats were used to investigate aging-related tubular cell apoptosis in the setting of renal I/R injury. The renal I/R model was induced by clamping bilateral renal arteries for 30 minutes followed by reperfusion for 18 hours. Cyclosporine A (CsA, 2 mg/kg) or mycophenolate mofetil (MMF, 20 mg/kg/d) was used before ischemia. Age-matched sham-operated rats served as controls. We found that tubular cell apoptosis increased more significantly in aged rats than in young rats after renal I/R. More pronounced increases of Bax/Bcl-2 ratio, cytosolic cytochrome c, and caspase-9, which are involved in mitochondria-mediated apoptosis, were found in aged rats than in young rats, and were associated with a more pronounced decrease in superoxide dismutase activity and increase of malondialdehyde content. However, increases of tumor necrosis factor-alpha and caspase-8, two components of death receptor-mediated apoptosis, showed no aging-related differences. Interfering mitochondria and death receptor pathways with CsA and MMF, respectively, reduced the apoptosis in both age groups, whereas CsA was more effective in aged rats. Our results have demonstrated that there was an aging-related increase of tubular cell apoptosis in the renal I/R model, which may be, at least partly, due to an enhanced mitochondrial pathway resulting possibly from increased oxidative stress.

Aging↗

PubMed2005

Effects of alterations of glomerular fibrin deposition on renal inflammation in rats at different age stages.

Recent data indicated that aging accelerated glomerular fibrin deposition induced by lipopolysaccharide (LPS) in mice. Our hypothesis was that aging may exacerbate glomerular inflammatory responses induced by glomerular fibrin deposition. Both young and aged rats with glomerular fibrin deposition induced by LPS were treated with tranexamic acid (TA) and TA plus urokinase (UK). Infiltrating inflammatory cells and expressions of monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular endothelial-cadherin were markedly upregulated in the LPS+TA group compared with the LPS group. Reduction of fibrin deposition in the LPS+TA+UK group was associated with downregulation of the above indices (p < .05), whereas the alteration of vascular endothelial-cadherin protein expression was negatively correlated with the fibrin deposition. There were also significant differences in increased expressions of monocyte chemoattractant protein 1 and intercellular adhesion molecule 1 between young and aged rats. These in vivo data demonstrated that fibrin deposition contributed to glomerular inflammatory responses, which could be exacerbated by aging.

Aging↗

PubMed2003

[Safety surveillance and management of specimen associated with SARS in clinical laboratory].

OBJECTIVE: To avoid the staff's infection and environmental contamination, we establish the rules suited for severe infectious disease in our laboratory. METHODS: (1) Enhance the staff's notion of safety, institute a rule for biological safety and make sure the responsibility of safety for everybody. (2) Set up a special laboratory or area for detection of specimens associated with SARS, appoint the staff specially assigned for the task. The approach to environmental cleaning and disinfection in the laboratory is according to the guidance. (3) Laboratory staff should take precaution when entering and leaving laboratory according to the guidance. (4) Collection, transportation, pre-disposal and storage of specimen from patients with SARS for testing should be done in leak-resistant environment. These specimen should be performed in biological safety cabinet. All Clinical waste must be placed in an appropriate leak-resistant biohazard bag or container, labeled and disposed of safely. RESULTS: Since the outbreak of SARS, no staff was infected with SARS in our clinical laboratory. CONCLUSION: Our precaution is feasible and effective. A series of rules ensure the safety for the laboratory staffs and environment.

Adult↗

PubMed2003

STAT proteins mediate angiotensin II-induced production of TIMP-1 in human proximal tubular epithelial cells.

BACKGROUND: Angiotensin II and tissue type inhibitor metalloproteinase-1 (TIMP-1) have been implicated in renal tubulointerstitial fibrosis, but the exact mediating signaling pathway is still unknown. Angiotensin II has been reported to activate signal transducers and activators of transcription (STAT) and induce proliferation of myocyte and vascular smooth muscle cells (VSMC). We hypothesized that the STAT signal pathway is involved in the process of renal tubulointerstitial fibrosis. Therefore, we designed the present study to explore whether angiotensin II could induce TIMP-1 expression in human proximal tubular epithelial cells, and whether it was mediated through the STAT signaling pathway. METHODS: Electrophoretic mobility shift assay (EMSA) was employed to determine the DNA-STAT binding activity. Supershift assay was used to test the components of activated STAT proteins. Nuclear translocation of activated STATs was observed with laser scanning confocal microscopy. TIMP-1 expression was analyzed with Northern and Western blots. Valsartan and PD123319 were used to block the effects of angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors of angiotensin II, respectively. RESULTS: Cultured human proximal tubular epithelial cells constitutively expressed TIMP-1. Angiotensin II induced TIMP-1, mRNA, and protein expressions in time- and dose-dependent manners, which could be inhibited by the AT1 receptor antagonist valsartan, but not by the AT2 antagonist PD123319. Angiotensin II also activated STAT-DNA binding activity in both dose-dependent and biphasic time-dependent manners, and increased the phosphorylation and nuclear translocation of STAT proteins. To examine the role of STAT in angiotensin II-induced TIMP-1 expression, STAT1 and STAT3 antisense oligonucleotides were used. Northern and Western blots showed that STAT1 and STAT3 antisense oligonucleotides could inhibit angiotensin II-induced TIMP-1 expressions, and STAT1 and STAT3 proteins, respectively, could be supershifted by their polyclonal antibodies. CONCLUSION: STAT1 and STAT3 may, at least in part, mediate angiotensin II-induced TIMP-1 mRNA expression in human renal proximal tubular epithelial cells, implicating a role of the STAT signaling pathway in pathogenesis of renal tubulointerstitial fibrosis.

Angiotensin II↗

PubMed2003

Relationship between aging and renal high-affinity sodium-dependent dicarboxylate cotransporter-3 expression characterized with antifusion protein antibody.

Sodium-dependent dicarboxylate cotransporter (NaDC), which is responsible for the transportation of intermediates of the Krebs cycle, has been implicated in extending the life span of drosophila. In the present study, we cloned an intracellular domain segment of human kidney NaDC-3, which is 75% identical to that of the rat, constructed a polyclonal antibody against fusion protein of glutathione S-transferase (GST)-NaDC-3, and detected its renal expression changes with aging in both Wistar rats and normal humans. Western blot and immunohistochemistry confirmed the specificity of the antibody, and its location was found to be on the basolateral membrane of the renal proximal tubule. In addition, Western and Northern blots showed that NaDC-3 in kidneys significantly increased with age in Wistar rats. In healthy humans, renal NaDC-3 abundance also increased with age. Our results demonstrated that NaDC-3 expression was increased in aged Wistar rats and aged people, indicating that NaDC-3 may have a role in the process of kidney aging.

Aging↗

PubMed2002

STAT1 and STAT3 mediate thrombin-induced expression of TIMP-1 in human glomerular mesangial cells.

BACKGROUND: Thrombin exhibits numerous biological effects on glomerular resident cells, such as cell proliferation, release and synthesis of cytokines and collagen, expressions of metalloproteinases and their inhibitors, especially tissue inhibitor of metalloproteinase-1 (TIMP-1). However, the signaling mechanisms underlying these cellular events have not been fully elucidated. The present study was designed to examine the role of signal transducers and activators of transcription (STAT) in thrombin-induced TIMP-1 expression in human mesangial cells. METHODS: Cultured human glomerular mesangial cells were incubated with thrombin up to 12 hours. The effects of the antisense of STAT1 and antisense of STAT3 on stimulated TIMP-1 mRNA levels and DNA-binding activities of both STAT1 and STAT3 were determined using Northern blot, electrophoretic mobility shift assay (EMSA), and supershift assay. RESULTS: Cultured human mesangial cells constitutively expressed TIMP-1, and thrombin induced TIMP-1 gene transcription in a time- and dose-dependent manner. Hirudin, a specific inhibitor of thrombin, could block thrombin-induced TIMP-1 expression. Thrombin also induced STAT-DNA binding activity in a similar time- and dose-dependent manner. In order to examine the role of STAT in thrombin-induced TIMP-1 expression, STAT1 and STAT3 antisense oligonucleotides were used. EMSA showed that STAT1 and STAT3 antisense oligonucleotides could inhibit both thrombin-induced STAT-DNA binding activities and TIMP-1 mRNA expression; the supershift assay showed that the SIF band consisted of STAT1 and STAT3 proteins. CONCLUSIONS: Both STAT1 and STAT3 may be involved, at least in part, in thrombin-induced expression of the TIMP-1 gene in cultured human mesangial cells.

Cells, Cultured↗

PubMed2002

Inhibition of apoptosis in rat mesangial cells by tissue inhibitor of metalloproteinase-1.

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important inhibitor of extracellular matrix degradation. Recently, it was reported that TIMP-1 also could inhibit apoptosis in B type lymphocyte. This study was designed to examine the effects of TIMP-1 on mesangial cell apoptosis. METHODS: The full-length cDNA of TIMP-1 was cloned and used to construct two recombinant vectors, TIMP-1S and TIMP-1AS, encoding sense TIMP-1 and antisense TIMP-1, respectively. The vectors were transfected into rat mesangial cells (RMC) and their expressions detected by Northern and Western blotting. Apoptosis was induced by serum deprivation, and was monitored for DNA fragmentation by TUNEL assay and DNA laddering. In addition, the expression of endogenous TIMP-1, matrix metalloprotein-2 (MMP-2), and MMP-9, as well as apoptosis-related genes Bcl-2 and Bax were investigated. RESULTS: TIMP-1AS transfection induced a suppression of TIMP-1 expression accompanied by an earlier onset of apoptosis, and TIMP-1S transfection induced TIMP-1 over-expression accompanied by a much later onset of apoptosis. A neutralizing antibody of TIMP-1 restored the sensitivity of TIMP-1S-transfected RMC to serum deprivation, but a synthetic matrix metalloproteinase inhibitor BB-94 did not influence the sensitivity of TIMP-1S-transfected RMC to serum deprivation. Finally, TIMP-1 over-expression inhibited the expression of Bax but with no effect on the expression of Bcl-2. CONCLUSION: TIMP-1 inhibits the serum deprivation-induced apoptosis in RMC, in which Bax might be involved.

Animals↗

PubMed2002

[Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in IgA nephropathy].

OBJECTIVE: To explore the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the renal tissue of patients with IgA nephropathy. METHODS: Immunohistochemistry and in situ hybridization assays were applied to detect the expression of mRNA and protein of TIMP-1, as well as the protein expression of MMP-9 in renal tissue of 38 patients with IgA nephropathy. RESULTS: MMP-9 was normally expressed, at a low level, in the glomerular endothelial cells and visceral epithelial cells, as well as in tubular epithelial cells and walls of vessels. The expression of MMP-9 was significantly increased in mesangial proliferative glomeruli and interstitial vascular walls of IgA nephropathy patients (P < 0.001), but markedly decreased in sclerotic glomeruli and not apparently altered in the tubule. No expression of TIMP-1 could be detected in normal renal tissue. TIMP-1 was only slightly expressed in the mesangioproliferative glomeruli of IgA nephropathy patients. TIMP-1 expression was increased notably in partially sclerotic glomeruli, and most prominently expressed in tubulointerstitium (P < 0.01), mainly in tubular epithelial cells, interstitial cells, and vascular endothelial cells. The expression of TIMP-1 was distinctly associated with the level of serum creatinine (P < 0.05), tubulointerstitial fibrosis (P < 0.01), and tubulointerstitial infiltration of leukocytes (P < 0.01). MMP-9 expression did not correlate with proteinuria, but negatively correlated with serum creatinine levels (P < 0.05). CONCLUSION: The abnormal expressions of MMP-9 and TIMP-1 may contribute to the progression of IgA nephropathy.

Adult↗