http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
실험적 당뇨 흰쥐에서 사구체의 크기에 따른 유전자 발현의 차이
곽승재 ( Seung Jae Kwak ),정동섭 ( Dong Sub Jung ),김진주 ( Jin Ju Kim ),이금희 ( Jin Ji Li ),한승혁 ( Seung Hyeok Han ),이태희 ( Tae Hee Lee ),김동기 ( Dong Ki Kim ),이정은,문성진 ( Sung Jin Moon ),한대석 ( Dae Suk Han ),강신욱 ( Sh 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.2
목적: 최근 발달한 microarray를 이용하여 실험적 당뇨 병성 신병증 모델에서 신장 전체를 이용한 유전자 발현의 차이를 규명한 연구는 있었으나 당뇨 사구체만을 이용한 연구는 거의 없었으며, 더욱이 비후된 사구체에 대한 연구는 전무한 상태이다. 이에 본 저자는 실험적 당뇨 흰쥐로부터 분리한 사구체를 이용하여 microarray를 시행하여 초기 당뇨병성 신병증에서 사구체와 관련된 유전자를 알아보고자 하였다. 방법: 흰쥐의 복강 내에 streptozotocin (65 mg/kg)을 주사하여 당뇨를 유발시켰으며, 당뇨 유발 6주와 12주 후에 당뇨군과 대조군 각 10마리씩을 희생시켰다. 희생시킨 흰쥐에서 sieving technique을 이용해 사구체를 분리하였으며, 사구체의 크기에 따라 125 m 체공의 체에 걸린 사구체를 큰 사구체, 75 m 체공의 체에 걸린 사구체는 작은 사구체로 분류하였다. 사구체로부터 RNA를 추출한 후 Rat cDNA 5K chip을 이용한 microarray를 수행하였으며, 유의한 유전자는 significant analysis of microarray (SAM)을 이용하여 선별하였다. 결과: Microarray 실험을 통한 전체 유전자의 발현 패턴을 hierarchical clustering을 수행하여 관찰한 결과, 실험 6주 후에는 작은 당뇨 사구체와 대조군 사구체의 유전자 발현 양상이 유사하였던 반면에, 큰 당뇨 사구체와 작은 당뇨 사구체의 유전자 발현 양상은 서로 상이하였다. 이와 반대로, 12주 후에는 큰 당뇨 사구체와 작은 당뇨 사구체의 유전자 발현 양상이 유사하였던 반면에, 대조군 사구체와 당뇨군 사구체의 유전자 발현 양상이 서로 상이하였다. 6주 당뇨 흰쥐 에서 분리한 큰 당뇨 사구체와 작은 당뇨 사구체 사이에 발현 차이를 보인 유전자 중 큰 사구체에서 유전자 발현이 1.5배 이상 증가된 유전자는 149개이었으며, 발현이 감소된 유전자는 58개이었다. 12주 당뇨 흰쥐의 경우, 105개의 유전자 중 큰 당뇨 사구체에서 유전자 발현이 1.4배 이상 증가된 유전자는 26개, 발현이 감소된 유전자는 11개이었다. 결론: 이상의 결과로, 실험적 당뇨 흰쥐에서 분리한 사구체의 크기에 따라 유전자 발현에 차이가 있으며, 당뇨병 유병 기간에 따라 크기에 따른 유전자 발현의 차이가 변할 것으로 생각된다. Purpose: Although a few gene-profiling studies with whole renal tissue have been described in experimental diabetic nephropathy, there is only one microarray study using diabetic glomeruli. Furthermore, hypertrophic glomeruli have not been explored. The purpose of this study is to elucidate gene expression profiles of hypertrophic glomeruli in early diabetic nephropathy. Methods: Forty-male Sprague-Dawley rats were injected with diluent (N=20) or streptozotocin intraperitoneally (DM, N=20) and were sacrificed at 6- and 12-week. Glomeruli were isolated by sieving technique. Glomeruli from 125 and 75 m sieves were classified into large (hypertrophic, DM-LG) and small glomeruli (DM-SG), respectively. After RNA extraction, hybridization was performed on the Rat cDNA 5K chip in triplicate, and slides were analyzed. The significant genes were selected using significant analysis of microarray. Results: At 6-week, hierarchical clustering revealed that gene expression profiles of DM-LG were different from those of DM-SG, whereas DM-SG and C glomeruli showed similar gene expression pattern. In contrast, gene expression profiles at 12-week were similar between DM-LG and DM-SG, whereas C glomeruli showed different gene expression pattern from DM glomeruli. At 6-week, a total of 207 genes showed greater than 1.5-fold differential expression. 149 genes were upregulated, whereas 58 were downregulated in DM-LG. On the other hand, differential gene expression greater than 1.4-fold was observed in 37 genes at 12-week, upregulated in 26 and downregulated in 11. Conclusion: These results suggest that the gene expression profiles of DM-LG are different from DM-SG, and the gene expression patterns change with the progression of diabetic nephropathy.
실험적 신질환 : 실험적 당뇨 백서에서 proteasome inhibitor인 Bortezomib의 세포외 기질 축적에 대한 효과
강이화 ( Ea Wha Kang ),한승혁 ( Seung Hyeok Han ),최영춘 ( Ying Chun Cui ),정동섭 ( Dong Sub Jung ),이금희 ( Jin Ji Li ),이순하 ( Sun Ha Lee ),김승혜 ( Seung Hye Kim ),곽승재 ( Seung Jae Kwak ),박제현 ( Je Hyun Park ),유태현 ( Tae 대한신장학회 2008 춘계학술대회 초록집 Vol.28 No.1
고립성 현미경적 혈뇨 환자에서 신장 조직검사 시행 여부의 결정을 위한 요중 βig-h3의 유용성
문성진 ( Sung Jin Moon ),한승혁 ( Seung Hyeok Han ),김진주 ( Jin Ju Kim ),이금희 ( Jin Ji Li ),정동섭 ( Dong Sub Jeong ),곽승재 ( Seung Jae Kwak ),이정은 ( Jung Eun Lee ),김동기 ( Dong Ki Kim ),김현욱 ( Hyun Wook Kim ),장제현 ( Ja 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.6
Purpose : This study was undertaken to elucidate the usefulness of urinary βig-h3 concentrations in differential diagnosis of isolated microscopic hematuria patients. Methods : Seventy-seven patients, in whom renal biopsy was performed due to microscopic hematuria without proteinuria, were enrolled. The patients were divided into two groups, IgAN group (patients with IgA nephropathy, N=37) and NM group (patients with normal or minor change on renal biopsy, N=40), and the clinical characteristics and laboratory findings were compared between the two groups. TGF-β and βig-h3 concentrations in urine were determined by ELISA and were compared between the two groups. To establish the optimal cut-off value of βig-h3/creatinine (Cr) ratio for the diagnosis of IgA nephropathy, a receiver operating characteristic curve was constructed and the sensitivity and specificity were calculated. Results : A comparative analysis revealed no significant differences in age and sex ratio between the two groups. There were no differences in serum IgG, IgA, IgM, C3, and C4 levels between the two groups. The urinary βig-h3/Cr ratio was significantly higher in the IgAN group compared to the NM group (6.632.6 vs. 4.462.6 ng/mg, p<0.05), whereas there was no significant difference in the urinary TGF-/Cr ratio between the two groups (14.82.1 vs. 13.75.1 pg/mg, p>0.05). A cut-off βig-h3/Cr ratio 4.5 has a sensitivity of 85.0% and a specificity of 77.8%. Conclusion : The urinary βig-h3/Cr ratio was a good predictor for the diagnosis of IgA nephropathy. Therefore, renal biopsy should be considered in isolated microscopic hematuria patients with high urinary βig-h3/Cr ratio.
당뇨병 신증 : 실험적 당뇨병성 신증에서 사구체 크기에 따른 cyclin dependent kinase inhibitor (CDKi) 및 세포사멸연관 물질의 변화
정동섭 ( Dong Sub Jung ),이금희 ( Jin Ji Li ),곽승재 ( Seung Jae Kwak ),김승혜 ( Seung Hye Kim ),이순하 ( Sun Ha Lee ),박제현 ( Je Hyun Park ),한승혁 ( Seung Hyeok Han ),유태현 ( Tae Hyun Yoo ),한대석 ( Dae Suk Han ),강신욱 ( Shin 대한신장학회 2008 춘계학술대회 초록집 Vol.28 No.1
당뇨 백서에서 p38 Mitogen-Activated Protein Kinase 억제제 (FR167653)가 세극막 관련 단백의 발현에 미치는 영향
류동열 ( Dong Ryeol Ryu ),유태현 ( Tae Hyun Yoo ),정동섭 ( Dong Sub Jung ),곽승재 ( Seung Jae Kwak ),박제현 ( Je Hyun Park ),이순하 ( Sun Ha Lee ),이금희 ( Jin Ji Lee ),류정화 ( Jung Hwa Ryu ),유민아 ( Min A Yu ),김승정 ( Seung Ju 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.3
목적: 본 연구에서는 실험적 당뇨 백서에서 p38 MAPK 억제재가 단백뇨 발생 및 세극막 관련 단백의 발현 변화에 미치는 영향을 알아보고자 하였다. 방법: Sprague-Dawley 백서 32마리를 대상으로, 16마리는 streptozotocin (65 mg/kg)으로 당뇨를 유발시켰으며 (DM군), 16마리는 위약을 투여하였다 (C군). 각 군에서 8마리는 p38 MAPK 억제제인 FR167653을 5 mg/kg의 용량으로 6주간 매일 근주하였다 (C+FR,DM+FR). 당뇨 유발 6주 후 24시간 소변을 수집한 다음 희생시켜 신장을 적출한 후 사구체를 분리하였다. 24시간 뇨알부민 배설량은 ELISA로 측정하였으며, 사구체 내 nephrin, P-cadherin, 그리고 ZO-1의 mRNA와 단백 발현은 각각 real-time PCR과 Western blot으로 분석하였다. 결과: 당뇨 유발 6주 후 24시간 뇨알부민 배설량은 C군 (0.29±0.04 mg/day)파 C+FR군 (0.32±0.04 mg/day)에 비하여 DM군 (1.09±0.17 mg/day, p<0.05)에서 유의하게 증가되었으며, 이러한 증가는 FR167653 투여로 의미있게 억제되었다 (0.38±0.05 mg/day, p<0.05). 세극막 관련 단백 중 nephrin mRNA 및 단백 발현은 DM군에서 C군에 비하여 각각 1.9배, 1.6배 증가되었으며, 이러한 증가는 FR167653 투여로 각각 74%, 89% 억제되었다 (p<0.05). 반면에, FR167653은 DM군에서 발현이 감소된 P-cadherin과 발현이 증가된 ZO-1에 의의있는 영향을 미치지 않았다. 결론: 이상의 결과로, FR167653은 당뇨 백서에서 p38 MAPK 활성화를 효과적으로 억제하였고, 뇨알부민 배설을 유의하게 감소시켰으며, 이러한 효과는 nephrin의 발현 변화의 호전과 관련이 있을 것으로 생각된다. Purpose: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. Methods: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. Results: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli.
당뇨 백서 사구체 및 고포도당으로 자극한 족세포에서 싸이클로스포린이 P-cadherin의 발현에 미치는 영향
강신욱 ( Shin Wook Kang ),유태현 ( Tae Hyun Yoo ),김형종 ( Hyung Jong Kim ),최훈영 ( Hoon Young Choi ),김주성 ( Joo Seong Kim ),정동섭 ( Dong Sub Jung ),김진주 ( Jin Ju Kim ),곽승재 ( Seung Jae Kwak ),한승혁 ( Seung Hyeok Han ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.1
Purpose: We investigated whether Cyclosporin A (CsA) had the anti-proteinuric effect in diabetic rats and whether it was associated with the alteration of P-cadherin expression. Methods: Sprague-Dawley rats were injected with diluent (C, N=16) or streptozotocin intraperitoneally (DM, N=16). Eight rats in each group were treated with 10% ethanol or with 1.5 mg/kg/day of CsA (C+CsA and DM+CsA) for 6 weeks. Immortalized mouse podocytes were cultured in media with 5.6mM glucose (LG), LG+CsA (10-8 M), LG+TGF-β1, 30 mM glucose (HG), or HG+CsA. Real time-PCR and Western blot were performed for P-cadherin and TGF-β1 mRNA and protein expression, respectively, with sieved glomeruli and cell lysates. Results: Urinary albumin excretion was significantly higher in DM compared with C rats, and CsA treatment inhibited the increase in albuminuria in DM rats. Glomerular P-cadherin mRNA and protein expression in DM were decreased compared with C rats, and these decreases were significantly inhibited by CsA. Glomerular TGF-β1 mRNA and protein expression were higher in DM than C rats, and CsA treatment inhibited the increase in TGF-β1 expression in DM. P-cadherin mRNA and protein expression in HG and LG+TGF-β1 podocytes were lower than LG cells, and these HG-induced decrements were restored by CsA. Conclusion: CsA treatment reduces urinary albumin excretion in DM rats. P-cadherin expression is decreased under diabetic conditions, which is ameliorated by CsA. In addition, inhibition of the increase in glomerular TGF-β1 expression under diabetic conditions by CsA seems to restore the P-cadherin expression, resulting in the decrease in albuminuria.
장기간 고포도당으로 자극한 배양 족세포에서 안지오텐신 2 수용체 차단제에 의한 세포비후 차단과 세포주기 조절 단백의 차등 발현
박형천 ( Hyeong Cheon Park ),허종호 ( Zhong Gao Xu ),류동열 ( Dong Ryeol Ryu ),유태현 ( Tae Hyun Yoo ),정동섭 ( Dong Sub Jung ),김진주 ( Jin Ju Kim ),곽승재 ( Seung Jae Kwak ),이금희 ( Jin Ji Li ),한대석,강신욱 ( Shin Wook Kang ) 대한신장학회 2006 Kidney Research and Clinical Practice Vol.25 No.5