Biomedical subjects

I Ebihara

Publications and source records attributed to I Ebihara.

At least 91 records · Page 5Linked to original sources

PubMed1993

Growth factor gene expression in kidney of murine polycystic kidney disease.

The DBA/2FG-pcy mouse has a form of slowly progressive kidney disease that appears similar in many respects to that seen in the autosomal dominant form of human polycystic kidney disease. The aim of this study was to examine the mRNA expression of growth-related proteins in kidney obtained from DBA/2FG-pcy mice and control DBA/2 mice at 8, 16, and 30 wk of age. The mRNA levels encoding for proliferating cell nuclear antigen (PCNA), transforming growth factor (TGF)-beta, platelet-derived growth factor (PDGF)-A and PDGF-B chains, insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) were increased with the progression of cystic lesions in the kidneys of DBA/2FG-pcy mice. At 30 wk of age, mRNA levels of PCNA, TGF-beta, PDGF-A and PDGF-B chains, IGF-I, and bFGF were increased 5.4-fold, 4.8-fold, 4.4-fold, 3.8-fold, 3.7-fold, and 4.6-fold, respectively, compared with those of control DBA/2 mice. In contrast, mRNA levels for epidermal growth factor in kidney of DBA/2FG-pcy mice decreased with age as compared with those of DBA/2 mice. These results suggest that decreased epidermal growth factor mRNA expression and increased expression of PCNA, TGF-beta, PDGF-A and PDGF-B chains, IGF-I, and bFGF mRNA may contribute to the progression of cystic lesions in DBA/2FG-pcy mice.

Age Factors↗

PubMed1993

Extracellular matrix component mRNA expression in glomeruli in experimental focal glomerulosclerosis.

This study was designed to assess how the expression of genes for components of the extracellular matrix is altered in a model of focal glomerular sclerosis. In this model, a unilateral nephrectomy combined with injections of puromycin aminonucleoside induces a much higher incidence of focal glomerular sclerosis. Rats received puromycin aminonucleoside on days 0, 27, 34, and 41 and underwent unilateral nephrectomy on day 22. Control rats received physiologic saline injections with and without unilateral nephrectomy. Rats from each group were killed on days 48, 60, and 80. The steady-state levels of glomerular mRNA encoding type IV collagen, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, and type I and type III collagens were compared in both the puromycin aminonucleoside-treated and the control glomeruli. The mRNA levels encoding type IV collagen and laminin B1 and B2 were increased three-, two-, and twofold, respectively, on day 48 of focal glomerular sclerosis. These transcripts were further increased eight-, seven-, and eightfold, respectively, on day 80 compared with the control glomeruli (P < 0.01). In contrast, heparan sulfate proteoglycan mRNA levels were not increased on day 48 when the animals had marked proteinuria. However, the heparan sulfate proteoglycan mRNA levels did become elevated by day 60 and remained elevated thereafter. The expression of type I and type III collagen mRNA was increased 12- and 7-fold, respectively (P < 0.01), on day 80 in focal glomerular sclerosis rats compared with the controls. An immunofluorescence study revealed the accumulation of immunoglobulin M, C3, type IV collagen, laminin, heparan sulfate proteoglycan, and type I and type III collagens in the sclerotic area. These data indicate that changes in the mRNA levels for components of the basement membrane and interstitial collagen are associated with the development of glomerular sclerosis.

Animals↗

PubMed1993

Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETB receptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2. 1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-beta, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-alpha, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1993

mRNA expression of growth factors in glomeruli from diabetic rats.

Evaluations of glomerular mRNA levels encoding for PCNA, TNF-alpha, PDGF-A and -B chains, TGF-beta, IGF-I, bFGF, and EGF were made at 4, 12, and 24 wk after injection of STZ in Sprague-Dawley rats. The mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF increased with age in STZ-induced diabetic rats. At 24 wk after STZ injection, mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF were increased 3.8-fold, (P < 0.01), 4.2-fold (P < 0.01), 4.0-fold (P < 0.01), 5.2-fold (P < 0.001), and 3.6-fold (P < 0.01), respectively, in the glomeruli of diabetic rats when compared with control rats. In contrast, mRNA levels for IGF-I, PDGF-A chain, and EGF were not altered in glomeruli from diabetic and control rats throughout the experimental period. Insulin treatment partially ameliorated the increase in mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF in the glomeruli of diabetic rats. These data indicate that alterations in growth factor mRNA levels in glomeruli may be a manifestation of diabetic nephropathy, and that hyperglycemia or insulin deficiency may play a role in abnormal growth factor gene regulation.

Animals↗

PubMed1993

Increased interleukin 6 mRNA expression by peripheral blood T cells from patients with IgA nephropathy.

We investigated interleukin 6 (IL-6) mRNA expression in peripheral blood T-cells obtained from 36 patients with IgA nephropathy (IgAN), 36 patients with other glomerulonephritides and 24 healthy age-matched controls. The majority of patients with IgAN had increased IL-6 mRNA expression by their T cells; no IL-6 mRNA was detected in T cells obtained from patients with other glomerulonephritides or normal controls. A positive correlation was noted between the IL-6 mRNA level and quantity of protein excretion in the urine, histopathological findings, and renal function. However, there was no significant correlation between IL-6 mRNA expression and the IgA-immune complex titer, serum IgA level or blood pressure. mRNA levels in T cells obtained from patients with grade III or IV renal histopathological findings were significantly higher than in those with grade I or II histopathology. In addition, mRNA levels in T cells obtained from patients with more than 1.0 g/day proteinuria were markedly higher than those with less than 1.0 g/day proteinuria. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IL-6 mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormally regulated IL-6 mRNA expression in peripheral blood T cells may be associated with disease activity in IgAN.

Adolescent↗

PubMed1993

Low-protein diet attenuates increased gene expression of platelet-derived growth factor and transforming growth factor-beta in experimental glomerular sclerosis.

The present study was designed to assess whether platelet-derived growth factor (PDGF)-A and -B chain and transforming growth factor-beta (TGF-beta) mRNA expression in glomeruli are affected by a low-protein (6%) diet during the course of focal glomerulosclerosis (FGS). Puromycin aminonucleoside (PAN) was injected intraperitoneally in rats, and the right kidney was removed on day 22. The nephrotic rats received successive intraperitoneal injections of PAN on days 27, 34, and 41. Control rats were subjected to a sham operation on day 22. The PAN-injected rats were divided into two groups. Group 1 rats were fed a standard diet containing 22% protein, whereas group 2 rats were fed a low-protein diet containing 6% protein, starting on the same day as the first PAN injection. Rats were killed on days 0, 48, 60, and 80 after the initial PAN injection. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 73% on day 80. The PDGF-A and -B chain and TGF-beta mRNA levels increased significantly as glomerulosclerosis progressed. A positive correlation was noted between the PDGF and TGF-beta mRNA levels and the incidence of glomerular sclerosis. The low-protein diet reduced the prevalence of glomerular sclerosis (10% on day 80) and attenuated the abnormally high expression of PDGF-A and -B chain and TGF-beta genes in FGS glomeruli. These findings suggest that PDGF and TGF contribute to glomerulosclerosis and that a low-protein diet attenuates markedly the increased glomerular expression of the PDGF and TGF-beta genes in glomerular sclerosis.

Animals↗

PubMed1993

Gene expression for endothelins and their receptors in glomeruli of diabetic rats.

The present study was designed to assess levels of messenger RNA encoding for endothelin-1, endothelin-3, and endothelin receptors A and B in glomeruli of rats with streptozotocin-induced diabetes at 4, 12, and 24 weeks of age. In addition, streptozotocin-induced rats with diabetes were either treated with 8 to 14 units neutral protamine Hagedorn insulin daily to maintain moderate hyperglycemia (approximately 200 mg/dl) or left untreated to produce severe hyperglycemia (more than 400 mg/dl) during the 4-week study period. The messenger RNA levels for endothelin-1 in glomeruli of diabetic rats increased with the progression of diabetic nephropathy (4 weeks, 2.5 times control level, p < 0.01; 12 weeks, 3.8 times, p < 0.01; and 24 weeks, 5.3 times, p < 0.001. In contrast, messenger RNA levels for endothelin receptors A and B were not altered in glomeruli from diabetic and control rats throughout the experimental period. Messenger RNA for endothelin-3 in glomeruli from diabetic and control rats was not detected until 24 weeks of age. Insulin treatment partially ameliorated the increase in messenger RNA for endothelin-1 in the glomeruli of diabetic rats (0.3 times compared with diabetic rats without insulin treatment, p < 0.01), whereas insulin treatment did not affect messenger RNA for endothelin receptors A and B in diabetic glomeruli. These findings indicate that increased endothelin-1 messenger RNA in glomeruli may be a manifestation of diabetic nephropathy, and hyperglycemia or insulin-deficiency may play a role in abnormal endothelin-1 gene regulation.

Animals↗

PubMed1993

Increased mRNA expression encoding for medullasin in peripheral blood mononuclear cells from patients with IgA nephropathy.

We investigated mRNA expression for medullasin (an inflammatory serine protease in bone marrow cells) in peripheral blood mononuclear cells (PBMC) obtained from 36 patients with primary IgA nephropathy (IgAN), 30 patients with other types of primary glomerular disease, 18 patients with secondary IgA nephritis including lupus nephritis and hepatic glomerulosclerosis and 24 healthy age-matched controls. The majority of patients with IgAN (86%) showed elevated medullasin expression in PBMC, while no medullasin mRNA expression was detected in PBMC obtained from patients with other types of primary glomerular disease, secondary IgA nephritis or normal healthy controls. A positive correlation was noted between mRNA levels and urinary protein excretion. The medullasin mRNA expression in PBMC also correlated with the severity of the histopathologic changes in renal tissue obtained from patients with IgAN. All the patients with severe proteinuria (more than 3.0 g/day) showed strong [more than (++)] medullasin mRNA expression in their PBMC. In addition, all the patients with more than (++) medullasin mRNA expression are grade III or IV histopathological findings. These studies suggest that abnormally regulated medullasin gene expression in PBMC may be associated with the progression of primary IgAN.

Adult↗

PubMed1992

Renal platelet-derived growth factor gene expression in NZB/W F1 mice with lupus and ddY mice with IgA nephropathy.

The present study was carried out to determine how platelet-derived growth factor (PDGF)-A and -B chain mRNA expression correlate with disease activity in the renal cortex of NZB/W F1 mice, a model of systemic lupus erythematosus, and ddY mice, a model of IgA nephropathy. The PDGF-A and -B chain mRNA levels increased significantly as nephritis progressed in NZB/W F1 mice. In the renal cortex of ddY mice, however, the PDGF mRNA levels increased slightly with age. The PDGF mRNA levels in ddY mice were lower than those in NZB/W F1 mice. In the NZW control kidneys, the PDGF mRNA levels changed minimally throughout the experiments. A positive correlation was noted between PDGF mRNA levels and histopathological changes in renal tissues. At the onset of nephritis, NZB/W F1 mice were divided into two groups that received either methylprednisolone (MPSL) or saline injections for 5 months. The development of histopathological lesions and the increased PDGF mRNA levels were suppressed by MPSL treatment. These data suggest that PDGF plays a role in the progression of nephritis and that the beneficial effect of MPSL correlates with its ability to decrease the abnormally high PDGF mRNA levels seen in lupus nephritis.

Animals↗

PubMed1992

Perforin gene expression in T lymphocytes correlates with disease activity in immunoglobulin A nephropathy.

1. We studied perforin gene expression in T lymphocytes obtained from 26 patients with IgA nephropathy and from 15 healthy age-matched control subjects. 2. The majority of patients with IgA nephropathy (96%) had elevated perforin mRNA expression, whereas no perforin mRNA expression was detected in the T lymphocytes of normal control subjects. 3. A positive correlation was noted between perforin mRNA expression and urinary protein excretion. 4. Perforin mRNA expression correlated also with the histopathology in the renal tissue of patients with IgA nephropathy. 5. Sixty per cent of patients with grade III or IV histopathology had high perforin mRNA expression in T lymphocytes [more than (++)]. 6. These studies suggest that disregulation of perforin gene expression in T lymphocytes may be associated with the progression of IgA nephropathy and could be used as an indicator of disease activity.

Adolescent↗

PubMed1992

Glucocorticoid ameliorates altered gene expression of extracellular matrix components in kidneys of New Zealand black/white F1 mice.

1. We examined the effects of methylprednisolone on the levels of messenger RNA encoding for extracellular matrix components, including alpha 1(IV) collagen chain, laminin B1 and B2 chains, heparan sulphate proteoglycan and alpha 1(I) and alpha 1(III) collagen chains, and on the accumulation of these proteins in the renal cortex of New Zealand Black/White F1 mice. 2. At the onset of nephritis, at about 5 months of age, New Zealand Black/White F1 mice were divided in two groups that received either methylprednisolone or saline injections for 5 months. 3. The development of histological lesions and the glomerular deposition of IgG, IgM and C3 were suppressed by methylprednisolone treatment from 5 to 10 months of age. 4. The distribution and intensity of type IV collagen, laminin, heparan sulphate proteoglycan, type I collagen and type III collagen in renal cortex were decreased by the administration of methylprednisolone. 5. Levels of messenger RNA encoding for alpha 1(IV) collagen chain, laminin B1 and B2 chains, heparan sulphate proteoglycan and alpha 1(I) and alpha 1(III) collagen chains in the renal cortex of New Zealand Black/White F1 mice were significantly ameliorated at 8-10 months of age by methylprednisolone administration. 6. These results indicate that methylprednisolone treatment can serve as an effective therapeutic approach to abnormal extracellular matrix regulation in murine lupus nephritis.

Animals↗

PubMed1992

Gene expression of growth-related proteins and ECM constituents in response to unilateral nephrectomy.

To identify the specific regulatory mechanism associated with the events following unilateral nephrectomy, we measured the levels of mRNA encoding for extracellular matrix (ECM) constituents, for protooncogenes, and for proliferating cell nuclear antigen (PCNA) in renal cortex and glomeruli. One hour after left nephrectomy, c-jun and c-fos mRNA levels in renal cortex increased rapidly and then decreased rapidly to the control level, whereas c-myc and PCNA mRNA levels showed a slower and more sustained increase, with a peak at 6 h after nephrectomy, and then decreased to the control level after 7 days. mRNA levels for basement membrane components including alpha 1-chain of type IV collagen, laminin B1 and B2 chains, and heparan sulfate proteoglycan core protein were significantly increased in renal cortex at 12 h after nephrectomy, whereas those for interstitial collagens including alpha 1-chains of type I and type III collagen were unchanged following nephrectomy. On the other hand, the glomerular expression of all genes examined in this study showed little change during the experimental period. These results suggest that the time course of mRNA expression of ECM constituents is different from that of growth-related proteins in renal cortex and that glomerular mRNA levels for these components may not be associated with renal hypertrophy in the early stages following unilateral nephrectomy.

Animals↗

PubMed1992

Abnormal regulation of insulin-like growth factor gene expression in peripheral blood mononuclear cells from patients with IgA nephropathy.

We investigated insulin-like growth factor (IGF)-I and -II mRNA expression in peripheral blood mononuclear cells (PBMC) and T cells obtained from 31 patients with IgA nephropathy (IgAN), 43 patients with other types of glomerulonephritis and 16 health age-matched controls. The majority of patients with IgAN showed elevated IGF-I and -II mRNA expression in PBMC, while no IGF-I and -II mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. In T cells obtained from IgAN, other types of glomerulonephritis and normal controls, however, IGF-I and -II mRNA expression was not detected. A positive correlation was noted between IGF-I and -II mRNA levels and urinary protein excretion. IGF-I and -II mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgAN. Sixty-nine percent of patients with more than 1.0 g/day proteinuria showed strong [more than (++)] IGF-I and -II mRNA expression in their PBMC. Eighty-one and 76% of patients with grade III and IV histopathological findings, respectively, showed strong IGF-I and -II gene expression in their PBMC. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IGF-I and -II mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormal regulation of IGF-I and -II gene expression in PBMC may be associated with the progression of IgAN and may be useful as an indicator of disease activity.

Adolescent↗

PubMed1992

ECM gene expression and its modulation by insulin in diabetic rats.

The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.

Analysis of Variance↗

PubMed1992

[Proto-oncogene, proliferating cell nuclear antigen, perforin and growth factor gene expression in peripheral blood mononuclear cells from patients with IgA nephropathy].

IgA nephropathy, which is widely recognized as one of the most common primary glomerulonephritides, is characterized by the constant presence of IgA in the glomerular mesangium. We investigated proto-oncogenes, proliferating cell nuclear antigen (PCNA), perforin, platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) mRNA expression in peripheral blood mononuclear cells (PBMC) obtained from patients with IgA nephropathy, patients with other types of glomerulonephritis and healthy age-matched controls. The majority of patients with IgA nephropathy showed elevated c-myc, c-fos, c-jun, c-raf, PCNA, perforin, PDGF-B chain, and IGF-I and -II mRNA expression in PBMC, while no these mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. A positive correlation was noted between mRNA levels and urinary protein excretion. mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgA nephropathy. These studies suggest that abnormal regulation of proto-oncogenes, PCNA, perforin, PDGF and IGF gene expression in PBMC may be associated with the progression of IgA nephropathy and may be useful as an indicator of disease activity.

Gene Expression Regulation↗

PubMed1992

[Regulation of fibrillar and type IV collagen genes].

Control of collagen synthesis can be exerted through control of mRNA levels by regulating of gene transcription and RNA maturation or the stability of mRNA. For fibrillar collagen genes many of the cis-acting regulatory elements are located in a relatively small region 5' to the transcription start site. The exon structure of the type IV genes differs significantly from that of fibrillar collagen in that triple-helical exons show considerable divergence from the 54 bp motif. The first intron of the alpha 1 (IV) is shown to contain an enhancer that can activate promoter. To identify the cellular mechanisms that determine the tissue-specific expression of the different collagen genes, the mechanisms whereby these genes respond to various cytokines and hormones that influence their expression.

Basement Membrane↗

PubMed1992

Activated peripheral blood mononuclear cells in IgA nephropathy express platelet-derived growth factor B-chain messenger RNA.

We investigated platelet-derived growth factor (PDGF) A- and B-chain messenger RNA expression in peripheral blood mononuclear cells or T cells obtained from 26 patients with IgA nephropathy and 15 healthy age-matched control subjects. Most patients with IgAN (88%) showed elevated PDGF B-chain expression in peripheral blood mononuclear cells; no PDGF B-chain expression was detected in peripheral blood mononuclear cells of normal control subjects. In T cells from both patients with IgAN and normal control subjects, however, PDGF B-chain messenger RNA expression was not detected. A positive correlation was noted between PDGF B-chain messenger RNA levels and urinary protein excretion. The PDGF B-chain messenger RNA expression in peripheral blood mononuclear cells also correlated with histopathologic changes in renal tissue obtained from patients with IgAN. Sixty-five percent of patients with grade III or IV histopathologic findings showed strong PDGF B-chain gene expression in their peripheral blood mononuclear cells. We could not detect PDGF A-chain messenger RNA expression in either peripheral blood mononuclear cells and T cells obtained from patients with IgAN and from healthy control subjects. These studies suggest that abnormally regulated PDGF B-chain expression in peripheral blood mononuclear cells may be associated with the progression of IgAN and may be useful as an indicator of disease activity.

Adult↗

PubMed1991

Altered steady-state levels of mRNA coding for extracellular matrices in renal tissues of ddY mice, an animal model for IgA nephropathy.

Correlations between the steady-state mRNA levels of extracellular matrices using specific cDNA probes for the alpha 1 chain of type IV collagen (alpha 1 (IV) chain); laminin A, B1, and B2 chains; and heparan sulfate proteoglycan (HSPG); and glomerular injuries in ddY mice were evaluated. Eight-, sixteen- and forty-week-old ddY mice were used in this study. ICR mice of the same age served as control. Extracted total RNA of pooled kidneys was fixed on a filter and then hybridized with the cDNA probes. Renal cryostat sections were incubated with rabbit anti-mouse type IV collagen, laminin, and HSPG antisera and then stained with FITC-labeled goat anti-rabbit IgG antiserum. The sections were also stained with FITC-labeled goat anti-mouse IgA, IgM, IgG, and C3 antisera. In light microscopy, the average number of glomerular cells was calculated at each age. Increased expression of extracellular matrices genes for the alpha 1(IV) chain; laminin A, B1, and B2 chains; and HSPG was found in renal tissues of ddY mice. Staining of type IV collagen, laminin, and HSPG was observed in renal tissues of ddY mice at each age. Increased proteinuria in 40-week-old ddY mice might be related to the decrease in glomerular basement membrane HSPG which acts as the anionic sites in such areas. Marked proliferation and or expansion of glomerular cells and mesangial matrices were observed in 40 week-old-ddY mice. The intensity of IgA and C3 deposits in the glomeruli was parallel to the levels of mRNA for such components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗