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Takashi Taguchi

Publications and source records attributed to Takashi Taguchi.

43 records · Page 3Linked to original sources
PubMed2002

Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy.

Cisplatin is an effective antitumor drug, but nephrotoxicity has restricted its clinical use. Renal interstitial fibrosis is a major complication of cisplatin treatment, due to the increased accumulation of extracellular matrix (ECM) proteins. Ets-1 protein plays a role in matrix remodeling by regulating matrix-degrading enzymes. We studied the role of Ets-1, matrix metalloproteinase-1 (MMP-1), and interstitial collagen (type III) in experimental cisplatin nephropathy. Wistar rats ( n = 24) were treated with cisplatin (6 mg/kg), and killed on days 3, 7, and 14, along with control rats. By immunohistochemistry, a significant increase ( P < 0.02) in the number of Ets-1-positive cells (40.09 +/- 1.52) was detected in kidneys of cisplatin-treated rats on day 3, compared with the number in control rat kidneys (29.80 +/- 0.13). The number of Ets-1-positive cells decreased in kidneys from cisplatin-treated rats on days 7 (10.93 +/- 1.20) and 14 (12.16 +/- 0.60). The expression of MMP-1 showed a similar pattern, increasing on day 3, but decreasing on days 7 and 14. The decreased levels of Ets-1 and MMP-1 were associated with increased interstitial accumulation of collagen in kidneys of cisplatin-treated rats on day 14. Molecular interactions among Ets-1, MMP-1, and type III collagens might play a role in matrix remodeling in cisplatin nephropathy.

Animal Experimentation↗
PubMed2002

Severe arteriolar lesion mimicking drug-induced arteriolopathy in a long-term surviving renal allograft.

We report severe arteriolar lesion mimicking drug-induced arteriolopathy in a renal allograft of a 37-year-old Japanese male, who has been treated by conventional immunosuppressive therapy but not administered cyclosporin or tacrolimus for 16 years after renal transplantation. Renal biopsy also showed glomerular changes including transplant glomerulopathy and features of chronic vascular rejection. The cause of the arteriolar lesion remains uncertain. Although its pathogenesis may be multi-factorial, long-term usage of conventional immunosuppressive agents and/or vascular rejection may contribute to the occurrence of the arteriolar lesion. We propose that biopsy study is needed for further understanding of histopathological behaviours of renal grafts in long-term survivors.

Adult↗
PubMed2000

Renal expression of the Ets-1 proto-oncogene during progression of rat crescentic glomerulonephritis.

The ets-1 proto-oncogene is a member of the transcriptional factor family and was identified by homology to the v-ets oncogene. It was recently demonstrated that Ets-1 protein interacts with the promoter region of the genes coding for proteinases, including matrix metalloproteinase-1 (MMP-1), MMP-3, and urokinase-type plasminogen activator, suggesting that it may play an important role in the regulation of MMP expression. The role of the ets-1 proto-oncogene in advanced glomerular diseases, where extracellular matrix accumulation is observed, remains undefined. In this study, the expression of ets-1 mRNA and protein during the progression of rat crescentic glomerulonephritis was examined using immunohistochemical analysis, reverse transcription-PCR, and in situ hybridization. Passive accelerated anti-glomerular basement membrane-induced nephritis was induced in rats by intravenous injection of nephrotoxic serum. Rats were euthanized on day 7, 14, 21, 28, or 42. Immunohistochemical analysis demonstrated significant upregulation of Ets-1 protein expression in glomeruli and the interstitium in anti-glomerular basement membrane-induced nephritis. The numbers of Ets-1-positive cells were increased 8.8-fold on day 21 in glomeruli (1.2+/-0.1 cells/glomerular cross-section, P<0.001) and sixfold on day 28 in the interstitium (21+/-1.3 cells/mm(2), P<0.001), compared with control samples. Ets-1 protein was predominantly localized in glomerular epithelial cells, endothelial cells, and interstitial cells. A small number of vascular endothelial cells, macrophages, and T cells also expressed Ets-1 protein. MMP-3 deposition was upregulated and positive cells in the interstitium often coexpressed Ets-1, whereas only a few glomerular cells were positive for both MMP-3 and Ets-1 protein. The expression of ets-1 mRNA was also markedly increased in diseased kidneys. The distribution of ets-1 mRNA was similar to that of the protein. These results indicate that overexpression of the ets-1 proto-oncogene by phenotypically altered renal cells might be associated with the pathogenesis of rat crescentic glomerulonephritis.

Animals↗
PubMedDate not supplied

Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathy.

The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as alpha-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy.

Actins↗
PubMedDate not supplied

Enhanced expression of heat shock protein 47 in rat model of peritoneal fibrosis.

OBJECTIVE: Peritoneal fibrosis is one of the serious complications of continuous ambulatory peritoneal dialysis therapy and is characterized by collagen accumulation. Heat shock protein 47 (HSP-47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis; however, the involvement of HSP-47 in the progression of peritoneal fibrosis is not fully understood. DESIGN: To examine the serial pathological alterations caused by peritoneal fibrosis, we made an experimental model of peritoneal fibrosis by daily intraperitoneal injection of chlorhexidine gluconate (CG) in rats for 28 days and examined the expression of HSP-47 together with that of types I and III collagen, alpha-smooth muscle actin (aSMA), and ED-1 (a marker for macrophages) using immunohistochemistry. Rats treated with saline containing 15% ethanol were used as the control group. RESULTS: In the control group, the peritoneal tissue was slightly thickened and HSP-47 was expressed in the peritoneum at day 28. In the CG group, the peritoneal tissue serially became thickened and fibrotic. The expression of HSP-47 was evident in mesothelial cells and submesothelial connective tissue after day 7 of treatment with CG, and increased thereafter. The expression of types I and III collagen and aSMA was proportionally strengthened during our experiments. ED-1-positive cells were present in thickened areas with abundant proliferation of collagen fiber. The number of cells positive for ED-1 increased gradually and reached a maximum at day 21. CONCLUSION: Our results indicate that, in a rat experimental model of peritoneal fibrosis, the expression of HSP-47 is associated with the progression of peritoneal fibrosis.

Animals↗