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Biomedical subjects

Yoshito Naiki

Publications and source records attributed to Yoshito Naiki.

6 recordsLinked to original sources
PubMed2005

Possible effects of hepatocyte growth factor for the prevention of peritoneal fibrosis.

OBJECTIVE: Some patients who had carried out long-term continuous ambulatory peritoneal dialysis discontinued the treatment because of progressive peritoneal fibrosis. It has been previously reported that transforming growth factor-beta1 (TGF-beta1) is one of the factors that induces peritoneal fibrosis. Also, hepatocyte growth factor (HGF) plays a role in the prevention of fibrosis and in inhibiting TGF-beta1 production. In this study, we examined the effects of HGF on peritoneal fibrosis by TGF-beta1 induced by high concentrations of D-glucose. DESIGN: We transfected a full-length human HGF cDNA in an expression vector into human peritoneal mesothelial cells (HPMCs) using the calcium phosphate method. Transfected HPMCs were cultured with high concentrations of D-glucose solution and co-cultured with fibroblasts using a transwell system. Cell proliferation was determined using the Tetra Color One method. TGF-beta1 and HGF protein were measured by enzyme-linked immunosorbent assay. RESULTS: In addition to recombinant HGF, the growth inhibition of HPMCs by high concentration D-glucose or TGF-beta1 was significant. By transfecting HGF cDNA into HPMCs, growth inhibition by high concentration D-glucose was completely restored. Furthermore, the production of TGF-beta1 was also significantly decreased. CONCLUSION: These results suggested that exogenous HGF could possibly prevent peritoneal fibrosis.

Cell Proliferation↗
PubMed2003

Mutant type glutathione S-transferase theta 1 gene homologue to mTOR in myelodysplastic syndrome: possible clinical application of rapamycin.

In this study, we observed the expression of the GSTT-1 gene in patients with myelodysplastic syndrome (MDS) at the messenger RNA level. Reverse transcription-polymerase chain reaction (RT-PCR) for GSTT-1 was performed with a pair of primers complementary to the 5' coding section and the 3' coding section of the GSTT-1 cDNA for amplifying the 623-bp band. Among 20 patients with MDS, 8 patients showed the expected 623-bp band on RT-PCR, and 12 patients showed a 500-bp band on RT-PCR, indicating that a 123-bp sequence was deleted as a mutant of the GSTT-1 gene. Furthermore, a BLAST DNA search showed that the deletion of a 123 bp sequence creates a sequence that is 63% homologous to human FKBP-rapamycin associated protein (FRAP); this protein has been termed a mammalian target of rapamycin (mTOR). We respectively transfected the wild type and the mutant type GSTT-1 gene in an expression vector to two cell lines (K562 and HL-60). The stable transformants for the wild type and the mutant type GSTT-1 genes were made by G418 selection. Interestingly, rapamycin could induce significant growth inhibition of the stable transformants for mutant type GSTT-1, which was indicative of apoptosis, but not that of those for wild type GSTT-1. These results suggest that rapamycin could be included in the therapeutic modality for the patients with MDS who have the mTOR sequences in GSTT-1 gene.

Annexin A5↗
PubMed2002

[Possible role of soluble erythropoietin receptors in renal anemia].

Recombinant human erythropoietin(rHuEpo) is effective for the treatment of renal anemia associated with chronic renal failure(CRF). However, we have encountered some patients with CRF who have sometimes developed a resistance to rHuEpo. This resistance can be due to iron or folate deficiency, aluminum toxicity, hyperparathyroidism, or auto-antibodies for rHuEpo. In this study, we focused on the soluble erythropoietin receptor(sEpoR), which can bind to rHuEpo. To demonstrate the possibility that the sweeping of rHuEpo by sEpoR results in resistance to rHuEpo, we performed a bioassay using the rHuEpo-dependent cell line, UT7/EPO. The results showed that recombinant mouse sEpoR(rmsEpoR) can reduce the proliferation of UT7/EPO induced by rHuEpo in a dose-dependent manner. We consider that this cell line could be a useful tool in a bioassay to detect the inhibitory factor(s) against Epo. We selected sera from three groups of patients with renal anemia associated with CRF who were receiving hemodialysis three times a week: the first was a patient group that needed a high dose of rHuEpo(7,500-9,000 unit/dialysis), the second was a patient group that needed an intermediate dose of rHuEpo (4,500 unit/dialysis), the third was a patient group that needed a low dose of rHuEpo(below 1,500 unit/dialysis). Interestingly, the proliferation of UT7/EPO determined with [3H]-thymidine incorporation was reduced by the addition of sera from the first group, but not by the addition of sera from the third group. These results suggested that serum sEpoR may play an important role in signal transduction via EpoR on erythroid progenitor in CRF patients.

Adult↗
PubMedDate not supplied

Involvement of TGF-beta signal for peritoneal sclerosing in continuous ambulatory peritoneal dialysis.

BACKGROUND: Functional failure of the peritoneal membrane is the most serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD). Transforming growth factor-beta (TGF-ss) is one of the key mediators of fibrosis in some organs, and is thought to be involved in peritoneal alterations. In this study, we examined the role of TGF-beta1/TGF-ss receptors for human peritoneal mesothelial cells (HPMCs) and fibroblasts, and their interactions in CAPD patients. METHODS: HPMCs were cultured for 48 h in a medium containing normal- dose glucose (7 mM), high-dose glucose (30 mM) and mannitol as an osmotic agent, equal to 30 mM glucose. Cell proliferation was observed using the Tetra Color One assay. The concentration of TGF-beta1 in culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The expression of TGF-ss receptor types I and II was observed by flow cytometry. HPMCs and fibroblasts were co-cultured and assayed using transwell inserts in order to identify the effects of the high-concentration glucose solution. RESULTS: HPMC proliferation was inhibited by the high concentration of glucose but not by mannitol. The inhibition was abrogated by the neutralizing antibody for TGF-beta1. TGF-beta1 was induced by a high concentration of glucose but not by mannitol. The expression of both TGF-ss receptors was augmented in culture with the high concentration of glucose but not with mannitol. In the co-culture assay, the number of HPMCs was decreased and fibroblasts were significantly increased in culture with the high concentration of glucose. CONCLUSIONS: A high concentration of glucose induced a large amount of TGF-beta1 and enhanced the expression of TGF-ss receptors. HPMCs were sensitive to TGF-beta1 in response to a high concentration of glucose. These data suggest that TGF-beta1 from HPMCs exposed to a high concentration of glucose down-regulates the proliferation of HPMCs and accelerates peritoneal fibrosis.

Cell Division↗