• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.215-221
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• 2010

Purpose : Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (${\leq}4$ and >$4mg/m^2/h$, ${\leq}40$ and >$40mg/m^2/h$, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>$4mg/m^2/h$) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-.66, P <0.001; dominant model OR 0.35, 95% CI 0.17-.69 P =0.002; recessive model OR 0.12, 95% CI 0.01-.06 P =0.025). Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

• Childhood Kidney Diseases
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• v.4 no.2
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• pp.127-135
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• 2000

Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. Methods: 36 Fischer-344 rats were divided into 6 goups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues me sampled for the observation of histological changes. Results: No differences in blood CsA level & serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V (P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles were more severe in tile LSD group. But, no differences were observed between tile groups treated with CsA and ACEI, and the groups treated with only CsA. Conclusion: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. further studies are required to elucidate whether Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.222-229
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• 1999

Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.

• Childhood Kidney Diseases
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• v.8 no.2
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• pp.149-158
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• 2004

Purpose : In order to evaluate the value of the renal expression of ICAM-1 as a marker of renal injury, we analyzed the relationship between abnormal tubular expression of ICAM-1 and histopathological features and clinical manifestations in children with IgA nephropathy (IgAN). Methods: The clinical data from 43 patients with IgAN were analyzed retrospectively and compared to the histopathologic subclassification proposed by Haas. ICAM-1 in tubular epithelium was assessed using the LSAB(Labeled streptavidine biotin) kit on the renal biopsy specimens. Results: In 43 patients with primary IgAN, 28 males and 15 females aged $12.2{\pm}2.2$ years were studied. There were no differences of renal tubular expression of ICAM-1 between patients with gross hematuria and without gross hematuria. But renal tubular expression of ICAM-1 in patients with proteinuria was significantly higher than that of in patients without proteinuria($78.2{\pm}14.19%\;vs\;55.8{\pm}32.20%,\;P<0.05$). Renal tubular expression of ICAM-1 was also associated with the severity of histopathological degree using Haas classification method. In subclass I, renal tubular expression of ICAM-1 was significantly lower than those of other subclasses. A significant correlation was found between the tubular expression of ICAM-1 and the total amount of protein in 24 hour collected urine$(r_s=0.47236,\;p<0.05)$. But there were no significant correlations between the renal tubular expression of ICAM-1 and interstitial cellular infiltration, tubular atrophy, and interstitial fibrosis respectively(F=0.89, P>0.05; F=0.31, p>0.05; F=0.21, p>0.05). Conclusion: Renal tubular expression of ICAM-1 can be a useful marker of renal injury in children with IgAN. (J Korean Soc Pediatr Nephrol 2004;8:149-158)

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.92-100
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• 2013

Purpose: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Sch$\ddot{o}$nlein purpura nephritis (HSPN). Methods: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. Results: The mean protein to creatinine ratio decreased from $3.7{\pm}1.5$ to $0.6{\pm}0.4$(P <0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. Conclusion: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.

• Korean Journal of Poultry Science
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• v.46 no.1
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• pp.31-37
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• 2019

A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.