Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Tetsuo Morioka is active.

Publication


Featured researches published by Tetsuo Morioka.


American Journal of Pathology | 2002

Up-Regulation of Connexin43 in Glomerular Podocytes in Response to Injury

Eishin Yaoita; Jian Yao; Yutaka Yoshida; Tetsuo Morioka; Masaaki Nameta; Takuma Takata; Junichi Kamiie; Hidehiko Fujinaka; Takashi Oite; Tadashi Yamamoto

Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of focal segmental glomerulosclerosis. However, it is poorly understood how podocytes respond to injury. In this study, glomerular expression of connexin43 (Cx43) gap junction protein was examined at both protein and transcript levels in an experimental model of podocyte injury, puromycin aminonucleoside (PAN) nephrosis. A striking increase in the number of immunoreactive dots with anti-Cx43 antibody was demonstrated along the glomerular capillary wall in the early to nephrotic stage of PAN nephrosis. The conspicuous change was not detected in the other areas including the mesangium and Bowmans capsule. Immunoelectron microscopy showed that the immunogold particles for Cx43 along the capillary wall were localized predominantly at the cell-cell contact sites of podocytes. Consistently, Western blotting and ribonuclease protection assay revealed a distinct increase of Cx43 protein, phosphorylation, and transcript in glomeruli during PAN nephrosis. The changes were detected by 6 hours after PAN injection. These findings indicate that the increase of Cx43 expression is one of the earliest responses that have ever been reported in podocyte injury. To show the presence of functional gap junctional intercellular communication (GJIC) in podocytes, GJIC was assessed in podocytes in the primary culture by transfer of fluorescent dye, Lucifer yellow, after a single-cell microinjection. Diffusion of the dye into adjacent cells was observed frequently in the cultured podocytes, but scarcely in cultured parietal epithelial cells of Bowmans capsule, which was compatible with their Cx43 staining. Thus, it is concluded that Cx43-mediated GJIC is present between podocytes, suggesting that podocytes may respond to injury as an integrated epithelium on a glomerulus rather than individually as a separate cell.


Circulation Research | 2003

ATP-Dependent Mechanism for Coordination of Intercellular Ca2+ Signaling and Renin Secretion in Rat Juxtaglomerular Cells

Jian Yao; Michihiro Suwa; Bing Li; Kazuko Kawamura; Tetsuo Morioka; Takashi Oite

Abstract— A change in intracellular Ca2+ is considered to be the common final signaling pathway through which renin secretion is governed. Therefore, information relating to the generation, control, and processing of Ca2+ signaling in juxtaglomerular cells (JG) will be critical for understanding JG cell behavior. In this study, we investigated the means by which JG cells harmonize their intracellular Ca2+ signals and explored the potential role of these mechanisms in renin secretion. Mechanical stimulation of a single JG cell initiated propagation of an intercellular Ca2+ wave to up to 11.9±4.1 surrounding cells, and this was prevented in the presence of the ATP-degrading enzyme, apyrase (1.7±0.7 cells), or by desensitization of purinergic receptors via pretreatment of cells with ATP (1.8±0.9 cells), thus implicating ATP as a mediator responsible for the propagation of intercellular Ca2+ signaling. Consistent with this, JG cells were demonstrated not to express the gap junction protein connexin43, and neither did they possess functional gap junction communication. Furthermore, massive mechanical stretching of JG cells elicited a 3-fold increase in ATP release. Administration of ATP into isolated perfused rat kidneys induced a rapid, potent, and persistent inhibition of renin secretion, together with a transient elevation of renal vascular resistance. ATP (1 mmol/L) caused up to 79% reduction of the renin secretion activated by lowering the renal perfusion flow (P <0.01). Taken together, our results indicate that under mechanical stimulation, ATP functions as a paracellular mediator to regulate renin secretion, possibly through modulating intra- and intercellular Ca2+ signals.


Nephron Experimental Nephrology | 2004

Effect of High Glucose on Nitric Oxide Production and Endothelial Nitric Oxide Synthase Protein Expression in Human Glomerular Endothelial Cells

Mari Hoshiyama; Bing Li; Jian Yao; Takashi Harada; Tetsuo Morioka; Takashi Oite

Background: Hyperglycemia directly contributes to the development of diabetic nephropathy. Nitric oxide (NO), a potent endothelium-derived vasodilator, has been suggested to participate in the regulation of renal blood flow, glomerular filtration rate, and mesangial matrix accumulation. Human vascular endothelial cells are known to exhibit functional heterogeneity, this prompted us to do the first study of NO bioavailability in human glomerular endothelial cells (HGECs), in response to high glucose exposure. Methods: NO release was examined by detecting nitrite generation by the Griess assay in HGECs exposed to control-level (5.5 mM) and high-level (15, 30 and 60 mM) glucose solutions at various time periods (24, 48 and 72 h) in the presence or absence of L-arginine (1 mM), or superoxide dismutase (SOD) (250 U/ml). In addition, we evaluated the effect of glucose on the expression of endothelial nitric oxide synthase (eNOS) in HGECs by Western blotting. Results: Final levels of nitrite generated in HGECs were reduced significantly, in a time- and concentration-dependent manner, after high glucose exposure. However, Western blot analysis revealed that eNOS protein expression was significantly upregulated at 12 h after exposure to high glucose concentrations (30 mM), reaching a peak at 48 h (twofold increase over baseline levels). The inhibitory effect of high glucose on NO production was restored by the addition of SOD. Addition of L-arginine (1 mM) to external media also reversed the inhibitory effect of high glucose on NO production of HGECs as well. Conclusions: The present study demonstrated that high glucose increased eNOS protein expression, but decreased NO release finally. Decreased NO bioavailability seems to be associated with overproduction of superoxide and L-arginine deficiency. These findings provide an important clue in clarifying the molecular basis of the mechanisms by which elevated glucose leads to an imbalance between NO and superoxide, resulting in impaired endothelial function. In addition, restoration of NO function by both administration of L-arginine and adequate intake of antioxidants suggests a potential supportive treatment for patients with diabetic nephropathy.


Clinical and Experimental Immunology | 2008

Progressive renal lesions induced by administration of monoclonal antibody 1-22-3 to unilaterally nephrectomized rats

Q.L. Cheng; Michiaki Orikasa; Tetsuo Morioka; Hiroshi Kawachi; X.M. Chen; Takashi Oite; Fujio Shimizu

A new animal model of progressive glomerulosclerosis was developed by administering a single i.v., injection of MoAb 1–22–3 to unilaterally nephrectomized rats. Renal morphological analysis revealed that glomerular lesions characterized by mesangial cell proliferation and mesangial matrix expansion were induced in about 95% of the glomeruli. Approximately 20% of the glomeruli of the unilaterally nephrectomized rats showed sclerosis or segmental sclerosis by week 6 after MoAb injection and crescent formation was observed in some glomeruli (ca 4%). Cellular infiltration was also noted in some parts of the interstitium. Increased expression of transforming growth factor–beta (TGF‐β) was observed in the unilaterally nephrectomized rats treated with MoAb 1‐22‐3, but we could not demonstrate pathological involvement of platelet‐derived growth factor (PDGF). even though early‐stage mesangial cell proliferation was observed. The mechanism of mesangial cell proliferation in this model remains to be elucidated. The relatively short period of time needed to induce the sclerotic changes is considered to be a great advantage of this model for clarifying the mechanisms involved in the chronic progression of mesangial proliferative glomerulonephritis.


Clinical and Experimental Immunology | 2008

Quantitative studies of monoclonal antibody 5-1-6-induced proteinuric state in rats

Hiroshi Kawachi; Katsuyuki Matsui; Michiaki Orikasa; Tetsuo Morioka; Takashi Oite; F. Shimizu

Murine monoclonal antibody (MoAb) 5‐1‐6 was already reported to bind to epithelial cell fool processes and to cause proteinuria in rats. In vivo kinetics of the injected MoAb 5‐1‐6, relationship between the quantity of kidney‐binding antibody and proteinuria. and changes in the amount of antigenic molecule recognized by this MoAb in the proteinuric state were studied. The amount of total kidney‐binding antibody (TK Ab) as determined I h after a 2 mg administration was 50.8 ± 10.4 μg/2 kidneys, and TKAb declined to 1.9 ± 0.4 at day 15. The minimum dose of MoAb required to induce proteinuria was 125 μg as the injected dose. This dose corresponded to 12‐8 μg of TKAb at I h and 0.34 μg of TKAb at day 5. The amount of MoAb 5‐1 ‐6 binding to isolated normal glomeruli was also shown to exceed 147‐7 μg/76000 glomeruli, indicating proteinuria to be induced provided more than 8.7% (= 12.8/147.7) of the critical epitopes is specifically occupied by MoAb. The total amount of MoAb 5‐1‐6 bound to glomeruli in vivo and in vitro was assayed with [125I]‐labelled anti‐mouse IgG. The amount of [125I] anti‐mouse IgG bound to glomeruli was 6.93 ± 0.45 μg/10 000 glomeruli from rat 5 days after this MoAb injection and 26.58 ± 0.66 μg/10000 control glomeruli, indicating the decrease in the number of MoAb 5‐1‐6‐rccognizcd antigen molecules in glomeruli isolated from the rat in proteinuric state induced by this MoAb. Thus, the MoAb 5‐1‐6‐recognized molecule itself may principally function to regulate the permeability of the glomerular capillary wall and the decrease of the molecule may lead to proteinuria.


Journal of The American Society of Nephrology | 2002

Coordination of Mesangial Cell Contraction by Gap Junction–Mediated Intercellular Ca2+ Wave

Jian Yao; Tetsuo Morioka; Bing Li; Takashi Oite

Gap junction intercellular communication (GJIC) plays a fundamental role in mediating intercellular signals and coordinating multicellular behavior in various tissues and organs. Glomerular mesangial cells (MC) are rich in GJ, but the functional associations of these intercellular channels are still unclear. This study examines the potential role of GJ in the transmission of intercellular Ca(2+) signals and in the coordination of MC contraction. First, the presence of GJ protein Cx43 and functional GJIC was confirmed in MC by using immunochemical staining or transfer of Lucifer yellow (LY) after a single cell injection, respectively. Second, mechanical stimulation of a single MC initiated propagation of an intercellular Ca(2+) wave, which was preventable by the GJ inhibitor heptanol but was not altered by pretreatment of MC with ATP or addition of apyrase into the assay system. Third, the phospholipase C (PLC) inhibitor U73122 could largely eliminate the mechanically elicited propagation of intercellular Ca(2+) waves, suggesting a possibly mediating role of inositol trisphosphate (IP(3)) in the initiation and transmission of intercellular Ca(2+) signaling. Fourth, injection of IP(3) into a single cell caused contraction, not only in the targeted cell, but also in the adjacent cells, as indicated by the reduction of cellular planar area. Fifth, addition of two structurally unrelated GJ inhibitors, heptanol and alpha-glycyrrhetinic acid (GA), into MC embedded in collagen gels significantly attenuated the reduction of gel areas after exposure to serum. This study provides the first functional evidence supporting the critical role of GJIC in the synchronization of MC behaviors.


Pediatric Nephrology | 2008

Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy

Masanori Takamatsu; Maki Urushihara; Shuji Kondo; Maki Shimizu; Tetsuo Morioka; Takashi Oite; Hiroyuki Kobori; Shoji Kagami

Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-β (TGF-β), α-smooth-muscle actin, glomerular cell number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid (mRNA) and protein expression in a dose- and time-dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-β production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop.


Nephron | 2002

Mechanisms and kinetics of Bowman's epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents

Yoshihide Fujigaki; Di Fei Sun; Taiki Fujimoto; Takayuki Suzuki; Tetsuo Goto; Katsuhiko Yonemura; Tetsuo Morioka; Eishin Yaoita; Akira Hishida

Background: We investigated the mechanisms and kinetics of Bowman’s epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents. Methods: Crescentic glomerulonephritis was induced by i.v. injection of rabbit anti-rat glomerular basement membrane antiserum in WKY rats. Results: Cellular crescents (83.5% of glomeruli) were first observed at day 7 after disease induction. Immunostaining of alpha-smooth muscle actin (alpha-SMA), as a marker for the myofibroblast phenotype, was found in some periglomerular regions as early as day 3, when it was also seen in parietal epithelial cells (PEC) of Bowman’s capsule at day 5 and in crescent formation at day 7. Proliferation marker Ki67-positive PEC was found at day 3, and double Ki67- and alpha-SMA-positive PEC could be seen at day 5. The migratory figure of PEC with the expression of alpha-SMA was found by immunoelectron microscopy. At day 7, some crescent cells were stained positive for PEC marker, protein gene product 9.5, in association with alpha-SMA or Ki67. Expression of transforming growth factor (TGF)-β receptor types I and II, as well as platelet-derived growth factor (PDGF) receptor β and PDGF-B increased in PEC as early as day 3. At day 5 marked deposition of cellular and common fibronectin, but not other extracellular matrix components examined was found in Bowman’s spaces where ED 1-positive macrophages infiltrated. Conclusions: PEC may be stimulated to proliferate and/or transdifferentiate into myofibroblast phenotype possibly by action of TGF-β and PDGF and/or binding of fibronectin to PEC, then migrate and/or proliferate, participating in glomerular crescents.


Nephron | 1998

Comparative Nephritogenicity of Two Monoclonal Antibodies That Recognize Different Epitopes ofRat Thy-1.1 Molecule

H. Nakayama; Takashi Oite; Hiroshi Kawachi; Tetsuo Morioka; Hideo Kobayashi; Michiaki Orikasa; Masaaki Arakawa; Fujio Shimizu

The pathophysiological role of the Thy-1.1 molecule expressed on rat mesangial cells with regard to mesangial cell dysfunction and injury remains unknown. The mechanism of Thy-1.1-associated injury has now been investigated with two monoclonal antibodies, 1-22-3 and OX7, that recognize different epitopes of Thy-1.1. Mesangiolysis and mesangial cell proliferation were more marked in rats injected with 1-22-3 than in those treated with OX7. Immunostaining for rat complement component C3 and also C9 was similar in the kidneys of rats 1 h after injection of either antibody. Alpha smooth muscle actin was first detected 3 days after injection of 1-22-3 and peaked on day 5; type I collagen staining showed a mesangial pattern on days 5 and 10. The staining for alpha smooth muscle actin and type I collagen was less intense in OX7-treated rats than in the 1-22-3-injected rats. The amounts of mRNAs encoding collagen types I and III peaked 5 days after injection of 1-22-3 and 10 days after injection of OX7. Rats injected with 1-22-3 developed proteinuria that was already marked on day 1 and peaked at 150 mg/day on day 3, whereas OX7 induced a low grade of proteinuria with large interindividual variability on day 3. Immunostaining for rat C3 in the normal rat kidneys, incubated in vitro with 1-22-3 or OX7 followed by incubation with normal rat fresh serum as a complement source, as well as the levels of serum complement activity, CH50, 30 min after injection of 1-22-3 or OX7 were similar, suggesting that the difference in the nephritogenicity of these two antibodies is not attributable to a difference in their complement-fixing activities, but rather may result from the difference in epitope specificities. The epitope recognized by 1-22-3 thus appears to be important in the initiation and progression of antibody-induced nephritis.


Clinical and Experimental Immunology | 1996

Anti-DNA antibody derived from a systemic lupus erythematosus (SLE) patient forms histone-DNA-anti-DNA complexes that bind to rat glomeruli in vivo

Tetsuo Morioka; Yoshihide Fujigaki; Stephen Batsford; R. Woitas; Takashi Oite; Fujio Shimizu; Arnold Vogt

Histone can mediate the binding of both free DNA and DNA complexed to anti‐DNA antibody to the glomerular capillary wall. We tested whether preformed histone–DNA–anti‐DNA immune complexes (IC) could bind to the glomerular capillary wall. The immune complex, generated with anti‐DNA antibody derived from an SLE patient and excess of 125I‐DNA followed by digestion with DNase, was mixed with histones. The complex containing 4 μg DNA was injected via the aorta into the left kidney of rats. At 15 min, 1.3% of the histone–DNA–anti‐DNA antibody complex bound (measured as 125I‐DNA), when histone was omitted less than 0.1% of the DNA–anti‐DNA antibody complex bound. By immunofluorescence human immunoglobulins and histones, representing the IC, could be observed in a capillary pattern; but no complement deposition was detected. Electron microscopy revealed discrete, electron dense deposits in a subendothelial, subepithelial and mesangial localization at 15 min. These results provide direct evidence that antibodies from serum of SLE patients can form soluble histone–DNA–anti‐DNA immune complexes that bind to the glomerular capillary wall in vivo

Collaboration


Dive into the Tetsuo Morioka's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Jian Yao

University of Yamanashi

View shared research outputs
Top Co-Authors

Avatar

Bing Li

Harbin Medical University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Arnold Vogt

University of Freiburg

View shared research outputs
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge