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Seiichi Matsuo

Publications and source records attributed to Seiichi Matsuo.

At least 37 records · Page 2Linked to original sources
PubMed2004

A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics.

Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. We developed a novel VEGF blockade system using RNA interference. The small interfering RNA (siRNA) targeting human VEGF almost completely inhibited the secretion of VEGF in a human prostate cancer cell line, PC-3, whereas the control scramble siRNA showed no effects. The VEGF siRNA with atelocollagen dramatically suppressed tumor angiogenesis and tumor growth in a PC-3 s.c. xenograft model. Atelocollagen provided a beneficial delivering means by which stabilization and efficient transfection of the siRNA injected into the tumors were achieved.

Animals↗
PubMed2004

Lack of the growth factor midkine enhances survival against cisplatin-induced renal damage.

Although cisplatin acts directly on proximal tubule epithelial cells and causes cell death, little is known regarding the biological significance of its secondary effects, such as inflammation. The growth factor midkine is highly expressed in the proximal tubule and exerts ambivalent activities as to cisplatin nephrotoxicity, ie, anti-apoptotic and chemotactic ones. Here we report that midkine-deficient mice show a significantly higher survival rate than wild-type mice. The levels of blood urea nitrogen and tubular degeneration and apoptosis were higher in wild-type mice despite the anti-apoptotic activity of midkine. We found that recruitment of neutrophils was more enhanced in wild-type mice, this being consistent with the chemotactic activity of midkine. Midkine expression in wild-type mice persisted for 24 hours, and then dramatically decreased. Preadministration of midkine anti-sense oligodeoxyribonucleotide to wild-type mice suppressed midkine expression, and consequently neutrophil infiltration. It is of note that neutrophil infiltration, apoptosis, and elevation of blood urea nitrogen became conspicuous sequentially, namely 1, 2, and 3 days after cisplatin administration, respectively. These findings suggest that early molecular events involving midkine induce inflammatory response and their circuits eventually enhance the death of the proximal tubule epithelial cells. The results indicate the crucial role of inflammation in cisplatin-induced renal damage, and provide a candidate molecular target for its prevention.

Animals↗
PubMed2004

In vivo gene transfer of endo-beta-galactosidase C removes alphaGal antigen on erythrocytes and endothelial cells of the organs.

BACKGROUND: The presence of Galalpha1-3Galbeta1-4GlcNAc (alphaGal) in pigs is a formidable barrier for pig-to-primate xenotransplantation. We have reported that administration of recombinant endo-beta-galactosidase C (EndoGalC) removes alphaGal on porcine erythrocytes and kidneys. The present study examined the effects of EndoGalC gene therapy on alphaGal suppression. METHODS: Naked plasmid DNA encoding Igkappa-EndoGalC was given to rats by rapid tail vein injection. The expression of alphaGal in the heart and kidney were studied by lectin staining followed by computer-assisted quantitative analyses. alphaGal expression on erythrocytes was determined by flow cytometric analyses. Enzymatic activity of EndoGalC in the serum was also determined by evaluating the capacity of EndoGalC in removing alphaGal epitopes. Elimination of alphaGal was further studied by injecting antibodies against alphaGal to rats 2 days after the gene transfer. RESULTS: Administration of 1 mg of Igkappa-EndoGalC/pCAGGS plasmid eliminated alphaGal from the vascular endothelium of the heart and kidney on day 1 and day 2. Between days 4 and 7, alphaGal started to reappear, but remained suppressed. No serious adverse effect was observed in rats treated with EndoGalC. Flow cytometric analyses showed that EndoGalC digested 97% of alphaGal on erythrocytes when measured 4 days after the gene transfer. Enzymatic activity of EndoGalC in the serum peaked on day 1, and significant levels were still observed on day 7. When antibodies against alphaGal were given, rats treated with EndoGalC showed no change, while all control rats died within 40 min. CONCLUSIONS: The present study demonstrates the potential of an EndoGalC gene transfer, using a hydrodynamics-based delivery system, in eliminating alphaGal from endothelial cells in vivo. The results also ensured that EndoGalC is not harmful suggesting that the production of pigs overexpressing EndoGalC would be a reasonable alternative to pigs deficient in alpha1,3galactosyltransferase.

Animals↗
PubMed2004

Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF.

BACKGROUND: Caveolin is a principal component of caveolae and regulates signaling in caveolae. Mesangial cells contain many caveolae, and thus manipulation of caveolin-1 expression level might be useful to control mesangial cell proliferation, which is an important aggravating factor in many renal diseases. METHODS: In the present study, we transfected caveolin-1 cDNA to rat primary mesangial cells and MES13 cells, and examined the effects on Raf-extracellular signal-regulated protein kinase (ERK) kinase (MEK)-mitogen-activated protein (MAP) kinase pathway and cell proliferation stimulated by basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF). Activity of the kinases was analyzed by immunofluorescence labeling and Western blot analysis. RESULTS: The overexpression of caveolin-1 inhibited the activation of Raf-1, MEK-1/2, and MAP kinase induced by either bFGF or PDGF. Furthermore, it suppressed the cell proliferation caused by the cytokines. The effect was specific to the Raf-MEK-MAP kinase pathway, because it did not influence activation of Smad2 induced by transforming growth factor-beta (TGF-beta). On the contrary, expression of a dominant-negative caveolin mutant, DGV-caveolin, augmented activation of MAP kinase. CONCLUSION: The result showed that overexpression of caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF. Because bFGF and PDGF are two major cytokines involved in the mesangioproliferative nephritis, the result implies that introduction of caveolin-1 expression vector is a potential therapeutic tool for the disease.

Animals↗
PubMed2004

A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.

A serine/threonine protein kinase, Cot/Tpl2, is indispensable for extracellular signal-regulated kinase (ERK) activation and production of TNF-alpha and PGE2 in LPS-stimulated macrophages. We show here that Cot/Tpl2 is also activated by other Toll-like receptor (TLR) ligands. Bacterial DNA rich in the dinucleotide CG (CpG-DNA), unlike LPS or synthetic lipopeptide, activated ERK in a Cot/Tpl2-independent manner. Peritoneal macrophages and bone marrow-derived DCs from Cot/Tpl2-/- mice produced significantly more IL-12 in response to CpG-DNA than those from WT mice. Enhanced IL-12 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, and the elevated IL-12 mRNA level in Cot/Tpl2-/- macrophages is accompanied by decreased amounts of IL-12 repressors, such as c-musculoaponeurotic fibrosarcoma (c-Maf) and GATA sequence in the IL-12 promoter-binding protein (GA-12-binding protein; GAP-12) in the nucleus. Consistently, Cot/Tpl2-/- mice showed Th1-skewed antigen-specific immune responses upon OVA immunization and Leishmania major infection in vivo. These results indicate that Cot/Tpl2 is an important negative regulator of Th1-type adaptive immunity, that it achieves this regulation by inhibiting IL-12 production from accessory cells, and that it might be a potential target molecule in CpG-DNA-guided vaccination.

Animals↗
PubMed2004

Simultaneous comparison of relative reactivities of twelve major anthocyanins in bilberry towards reactive nitrogen species.

The reactivities of twelve major anthocyanins identified in bilberry extracts towards nitric oxide (NO.) and peroxynitrite (ONOO-) were studied in vitro using capillary zone electrophoresis (CZE). The reactivities of the anthocyanins towards NO. were slightly weak compared with that of (+)-catechin as a reference antioxidant under anaerobic conditions except delphinidin glycosides (Dp3glys). The reactivities of other anthocyanins were not significantly affected by either the aglycon structure or the type of sugar moiety. Under aerobic conditions, all anthocyanins and catechin showed significant enhancement of the reactivity, indicating that they reacted with other reactive species secondarily generated from NO. . Dp3glys showed rather extraordinally high reactivity towards ONOO- compared to other anthocyanins which showed approximately two times low reactivity than catechin when compared with IC50. Structural divergence in the reactivity was also small for all these anthocyanins.

Anthocyanins↗
PubMed2004

Endotoxin-induced chemokine expression in murine peritoneal mesothelial cells: the role of toll-like receptor 4.

Acute peritonitis, in which peritoneal mesothelial cells are directly exposed to bacterial components, is a major cause of peritoneal dysfunction in continuous ambulatory peritoneal dialysis patients. We have previously shown that Toll-like receptors (TLR) are expressed in kidney cells, and LPS induces TLR4-dependent chemokine production in tubular epithelial cells. The present work was designed to investigate the involvement of TLR, especially TLR4, in the lipid A-mediated chemokine production by murine peritoneal mesothelial cells (MPMC). A primary cell culture of MPMC from C3H/HeN mice (wild-type mice; LPS sensitive) and from C3H/HeJ mice (containing a point mutation of TLR4; LPS hyposensitive) was established. The expression profile of the TLR family and their accessory molecules, CD14 and MD-2, which are requisite for the LPS signaling pathway, was examined by RT-PCR, Northern blot test, and immunohistochemical staining. Synthetic lipid A-mediated chemokine production by MPMC was studied. The involvement of MAP kinase family (ERK, JNK, and p38 mitogen-activated protein kinase) and nuclear factor (NF)-kappaB in these processes was also studied. MPMC constitutively express TLR4, CD14, and MD-2. A prominent induction of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein (MIP)-2 by MPMC was detected after lipid A stimulation and was strictly dependent on TLR4. Furthermore, TLR4-dependent chemokine production followed by leukocyte influx into the peritoneal cavity was also confirmed in vivo after stimulation with LPS. mRNA expression of MCP-1 was abolished by NF-kappaB inhibition, but were not affected by the inhibition of ERK, JNK, or p38. As compared with MCP-1, MIP-2 mRNA expression was inhibited by a high dose of curcumin but not by NF-kappaB decoy oligodeoxynucleotide and individual inhibitions of MAP kinase, suggesting that the additional signaling pathway with NF-kappaB might be involved in mRNA expression of MIP-2. These show that TLR4 is directly involved in the production of MCP-1 and MIP-2 by MPMC in a NF-kappaB-dependent manner, but the process does not require any MAP kinase activation. The results provide a candidate molecular target in prevention of it.

Animals↗
PubMed2004

[Focal segmental glomerulosclerosis].

Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome in adult as well as in the children. Untreated or steroid-resistant primary FSGS often shows a progressive renal insufficiency and reaches to end-stage renal failure. Concerning the treatment for such patients, the combined immunosuppressive therapy with corticosteroid and other cytotoxic drugs (cyclophosphamide, cyclosporine and tacrolimus etc.) is recommended. Since podocyte injury seems to be the most important primary events in FSGS, the extensive studies have been focused on the role of podocyte-related molecules. Recently slit membrane-associated molecules (CD2AP, alpha-actinin 4 and podocin) and angiotensin II type I receptor in the podocyte have been clearly shown to be relevant for the pathogenesis of FSGS.

Actinin↗
PubMed2003

Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis.

In the developing kidney, activation of the rearrangement during transfection tyrosine kinase by glial cell line-derived neurotrophic factor (GDNF) is required for normal branching of the ureteric bud epithelium [corrected]. By differential display analysis we identified a novel GDNF-inducible gene (named GZF1) with a BTB/POZ (broad complex, tramtrack, and bric-a-brac)/(poxvirus and zinc finger) domain and 10 tandemly repeated zinc finger motifs. The up-regulation of the GZF1 gene showed two peaks at 1 h and 24-48 h after GDNF stimulation by Northern blotting. The late induction was also found at protein levels by Western blotting with anti-GZF1 antibody. As observed for other proteins with the BTB/POZ domain, the GZF1 protein had strong transcriptional repressive activity. Intriguingly, its expression was detected at high levels in branching ureteric buds and collecting ducts of mouse metanephric kidney in which RET was also expressed. Antisense phosphorothioated oligodeoxynucleotides of the GZF1 gene markedly impaired the ureteric bud branching in the metanephric organ culture, suggesting that the induction of GZF1 expression via the GDNF/RET signaling system is required for renal branching morphogenesis.

Amino Acid Sequence↗
PubMed2003

The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids.

BACKGROUND: Although Aristolochia manshuriensis (AM), which was incriminated in the Japanese variety of Chinese herbs nephropathy, has been recently shown to be nephrotoxic in rats, less is known about whether this toxicity is attributable to its aristolochic acids (AA). We compared the renal effect of AM with that of Akebia quinata (AQ), which has similar components to AM but is free of AA; we also compared this effect of AM with that of pure AA, and studied its possible mechanism. METHODS: In study 1, rats were divided into four groups. Each group was orally given either 0.4 g of AM, 4 g of AM, or 4 g of AQ per day, or vehicle, for 5 days. In study 2, rats were given 4 g of AM (which contained 4 mg of AA), or 4 mg of pure AA per day, or vehicle, for 5 days. Renal function, and renal histology were evaluated on day 5 in study 1 and on days 1, 3, 5, and 14 in study 2. In study 2, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) staining were also performed. In study 3, rats were treated in the same way as in study 2, but were all killed on day 5. Concentrations of AA (I + II) were measured in serum and urine in study 2, and in the kidney, lung, heart, liver, and spleen in study 3. RESULTS: In study 1, only the rats that received 4 g/day of AM developed tubular necrosis, azotemia, proteinuria, and glucosuria. In study 2, both AM- and AA-treated rats showed progressive tubular damage, decreased renal function, and increased urinary protein excretion. The degree of these alterations was comparable in the AM and AA groups. Moreover, the concentrations of AA (I + II), in serum, urine, and kidney were also comparable in the AM- and AA-treated rats. High levels of AA were detected in the lung and kidney. Apoptotic tubular cells increased on day 5 and had decreased by day 14 after the withdrawal of AM or AA. Meanwhile, proliferating tubular cells progressively increased from day 3 to day 14. CONCLUSIONS: Our study indicates that the renal toxicity of AM can be attributed to its AA component. Tubular cell apoptosis might be one of the mechanisms involved in this renal injury.

Animals↗
PubMed2003

Implication of the complement system in the induction of anti-glomerular basement membrane glomerulonephritis in WKY rats.

In WKY rats, administration of a small dose of anti-glomerular basement membrane antibody induces severe crescentic glomerulonephritis, which is characterized by infiltration of CD8-positive lymphocytes and monocytes/macrophages into the glomeruli with crescent formation. In this study, the involvement of the complement system was examined in the induction of this model. To deplete complement, cobra venom factor (CVF) was used. By a single injection with CVF at 24 h prior to the induction of this model, plasma C3 level from days 0-2 was less than 10% compared with pre-injection of CVF. Complement was almost depleted in the early phase of this model. No significant differences were observed in proteinuria and the frequency of glomeruli associated with the extracapillary crescentic lesions between the CVF-treated group and the control group. In addition, the number of monocytes/macrophages and CD8-positive lymphocyte infiltration into the glomeruli showed no significant differences between both groups. These results indicate that the possibility of complement system involvement is considered low in the induction of this model.

Animals↗
PubMed2003

Non-dipping is a potent predictor of cardiovascular mortality and is associated with autonomic dysfunction in haemodialysis patients.

BACKGROUND: Lack of nocturnal blood pressure (BP) fall (non-dipping) is common among haemodialysis (HD) patients, but much less is known regarding its association with cardiovascular (CV) disease morbidity and mortality. METHODS: Eighty HD patients initially underwent 24 h ambulatory BP monitoring (ABPM), and then they were defined as either 'dippers' (n=24, nocturnal BP fall > or = 10%) or 'non-dippers' (n=56, fall <10%). Coronary angiography was performed in the patients who had signs and/or symptoms of coronary artery disease (CAD). Twenty-four hour ambulatory ECG was recorded in 20 dippers and 20 non-dipper HD patients, and in 20 normal subjects. All patients were followed for up to 5.8 years (33.0+/-19.1 months). The outcome events studied were the hospitalisations due to CV diseases and CV death. RESULTS: Compared with dippers, non-dippers initially had a higher incidence of coronary artery stenosis (P<0.05) along with left ventricular asynergy (both Ps<0.01). The circadian rhythm of autonomic function was impaired in non-dippers. The incidences of CV events and CV deaths were 3.5 and 9 times higher in non-dippers than in dippers. The cumulative CV event-free survival and CV survival rates were lower in non-dippers than in dippers (P=0.02 and P=0.005, respectively). Based on Cox analysis, non-dipping was associated positively with CV events and CV mortality [hazard ratio (HR) 2.46, 95% CI 1.02-5.92, P=0.038 and HR 9.62, 95% CI 1.23-75.42, P=0.031, respectively]. Meanwhile, nocturnal systolic BP fall, diurnal systolic BP and diurnal pulse pressure were negatively associated with CV event/death. The clinic BP was not associated with CV event/death. CONCLUSIONS: The non-dipping phenomenon is closely related to a high incidence of CV diseases, a poor long-term survival and profound autonomic dysfunction. ABPM is useful in predicting long-term CV prognosis in HD patients.

Aged↗
PubMed2003

Anti-monocyte chemoattractant protein-1 gene therapy attenuates renal injury induced by protein-overload proteinuria.

It has been postulated that protein filtered through glomeruli activates tubular epithelial cells, which secrete vasoactive and inflammatory substances including chemokines, leading to tubulointerstitial renal injury. The present study was designed to investigate the role of monocyte chemoattractant protein-1 (MCP-1) in this process and to evaluate the effectiveness of a kidney-targeted gene transfer technique using hydrodynamic pressure. Naked plasmid encoding 7ND (an MCP-1 antagonist) or a control plasmid was introduced into the left kidney of rats. Three days after gene transfer (day 0), intraperitoneal administration of bovine serum albumin (10 mg/g body wt per day) was started and continued for 14 or 21 d. RT-PCR showed that 7ND mRNA was expressed only in the gene-transfected kidney. Immunostaining showed that 7ND protein was localized in the interstitial cells. Macrophage infiltration was significantly reduced in the left kidney of rats treated with 7ND on days 14 and 21. In the right kidney, such effects were not observed. 7ND also attenuated tubular damage and decreased the number of apoptotic cells. Computer-assisted analysis revealed that the areas positively stained for alpha-smooth muscle actin (alpha SMA), fibronectin-EDA, type I collagen, and collagen fibrils were significantly reduced in the 7ND-treated kidney on day 21. Furthermore, 7ND gene therapy significantly reduced MCP-1 and TGF-beta 1 mRNA expression. These results demonstrate that MCP-1 plays an important role in the development of tubulointerstitial inflammation, tubular damage, and fibrosis induced by proteinuria. The fact that 7ND gene therapy had little effect on the contralateral kidney indicates that 7ND acted locally. This strategy may have a potential usefulness as a gene therapy against tubulointerstitial renal injury.

Animals↗
PubMed2002

Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells.

Pyelonephritis, in which renal tubular epithelial cells are directly exposed to bacterial component, is a major predisposing cause of renal insufficiency. Although previous studies have suggested C-C chemokines are involved in the pathogenesis, the exact source and mechanisms of the chemokine secretion remain ambiguous. In this study, we evaluated the involvement of Toll-like receptors (TLRs) in C-C chemokine production by mouse primary renal tubular epithelial cells (MTECs). MTECs constitutively expressed mRNA for TLR1, 2, 3, 4, and 6, but not for TLR5 or 9. MTECs also expressed MD-2, CD14, myeloid differentiation factor 88, and Toll receptor-IL-1R domain-containing adapter protein/myeloid differentiation factor 88-adapter-like. Synthetic lipid A and lipoprotein induced monocyte chemoattractant protein 1 (MCP-1) and RANTES production in MTECs, which strictly depend on TLR4 and TLR2, respectively. In contrast, MTECs were refractory to CpG-oligodeoxynucleotide in chemokine production, consistently with the absence of TLR9. LPS-mediated MCP-1 and RANTES production in MTECs was abolished by NF-kappaB inhibition, but unaffected by extracellular signal-regulated kinase inhibition. In LPS-stimulated MTECs, inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase significantly decreased RANTES, but did not affect MCP-1 mRNA induction. Thus, MTECs have a distinct expression pattern of TLR and secrete C-C chemokines in response to direct stimulation with a set of bacterial components.

Animals↗