72 research outputs found

    ์—ฌ์„ฑ, IMC, ๊ทธ๋ฆฌ๊ณ  ๋งˆ์ดํด๋Ÿฝ

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    ์ธํ„ฐ๋„ท์€ ์ƒˆ๋กœ์šด ์„ธ๊ณ„๋กœ์„œ ์˜ค๋Š˜๋‚  ์ „์ฒด ์‚ฌํšŒ ๊ฒฝ์ œ๋ฅผ ๋ฐ”๊พธ์–ด ๋‚˜๊ฐ€๊ณ  ์žˆ๋‹ค. ์ธํ„ฐ๋„ท์˜ ๋ฌดํ•œ์„ฑ. ๋ถˆํ™•์‹ค์„ฑ, ๊ฐ€์ƒ์„ฑ, ๊ฐœ๋ณ„์„ฑ, ํ‰๋“ฑ์„ฑ, ์ž์œ ์„ฑ์€ ๊ธฐ์กด ๊ตฌ์งˆ์„œ์˜ ์„ธ๊ณ„์™€ ๋™๋“ฑํ•˜๊ณ ๋„ ์–ด๋Š ์ผ๋ณ€์—์„œ๋Š” ์šฐ์›”ํ•œ ํŠน์ง•์„ ์ง€๋‹ˆ๊ณ  ์žˆ๋‹ค. ์ด๋Ÿฌํ•œ ์ธํ„ฐ๋„ท์˜ ํŠน์ •์„ ์ธํ„ฐ๋„ท๊ณผ ๊ด€๋ จ๋œ ์ผ๋ฐ˜ ํ™˜๊ฒฝ๊ณผ ์ธํ„ฐ๋„ท ๋‚ด๋ถ€์˜ ํ™˜๊ฒฝ์œผ๋กœ ์‚ดํŽด๋ณธ๋‹ค. ์ธํ„ฐ๋„ท ๋‚ด๋ถ€ํ™˜๊ฒฝ์€ ์ตœ๊ทผ ์ƒˆ๋กœ์ด ๋“ฑ์žฅํ•œ ์ธํ„ฐ๋„ท ์ƒํƒœ๊ณ„ ํ™˜๊ฒฝ์ด๋ก ์„ ํ†ตํ•ด ์šฐ๋ฆฌ ๊ณผ์ œ์˜ ์ฃผ์•ˆ์ ์ธ ํฌํ„ธ์‚ฌ์ดํŠธ์˜ ์ƒํƒœ๊ณ„์ƒ์˜ ์œ„์ƒ์„ ์ •๋ฆฝํ•œ ํ›„, ํฌํ„ธ์‚ฌ์ดํŠธ ์ž์ฒด์˜ ํŠน์„ฑ์„ ์‚ดํŽด ๋ณด๊ณ ์ž ํ•œ๋‹ค

    (์ฃผ)ํ•œ๊ธ€๊ณผ ์ปดํ“จํ„ฐ : ์ œ2์˜ ์‹ ํ™”์ฐฝ์กฐ๋ฅผ ์œ„ํ•˜์—ฌ

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    ์‚ฐ์—…์˜ ๊ฝƒ์€ ๋ฒค์ฒ˜๋‹ค๋ผ๋Š” ๋ง์€, ์ง€๊ธˆ๊นŒ์ง€๊ฐ€ ์‚ฐ์—…ํ˜๋ช…์„ ๊ธฐ๋ฐ˜์œผ๋กœ ํ•œ ๊ตด๋š์‚ฐ์—…์ด ์ง€๋ฐฐํ•˜๋˜ ์‹œ๋Œ€์˜€๋‹ค๋ฉด, ํ–ฅํ›„์˜ ์„ธ๊ธฐ๋Š” ๊ทธ์•ผ๋ง๋กœ ๋ฌดํ•œ๊ฒฝ์Ÿ์˜ ์‹œ๋Œ€์— ๋ฌด์—์„œ ์œ ๋ฅผ ์ฐฝ์กฐํ•˜๋Š” ๋ฒค์ฒ˜๊ธฐ์—…๋“ค์ด ์ง€๋ฐฐํ•˜๋Š” ์‹œ๋Œ€๊ฐ€ ๋  ๊ฒƒ์ž„์„ ๊ทน๋ช…ํ•˜๊ฒŒ ๋Œ€๋ณ€ํ•ด ์ค€๋‹ค. ๊ทธ ์ค‘์— ์„œ๋„ ๊ฝƒ ์ค‘์— ๊ฝƒ์œผ๋กœ ์ถ”์•™๋ฐ›๊ณ  ์žˆ๋Š” ์ธํ„ฐ๋„ท ๋น„์ฆˆ๋‹ˆ์Šค ๋ถ„์•ผ์˜ ๋ฒค์ฒ˜๊ธฐ์—…๋“ค์€ ์œ ๋ก€์—†๋Š” ๋ฒค์ฒ˜๋ถ์„ ์ผ์œผํ‚ค๋ฉด์„œ ๊ธ‰์†๋„๋กœ ํ™•์‚ฐ๋˜๊ณ  ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋””์ง€ํ„ธ ์‹œ๋Œ€์˜ ์ด์•„์ธ ๋ฒค์ฒ˜๊ธฐ์—…๋“ค์˜ ์‹ค์ฒด๊ฐ€ ๋‹จ์ง€ ์ผ์‹œ์ ์ธ ๋ฒ„๋ธ”(๊ฑฐํ’ˆ)์ผ ์ˆ˜ ์žˆ๋‹ค๋Š” ์šฐ๋ ค์™€ ํ•จ๊ป˜ ํ™ฉ๊ธˆ ์•Œ์„ ๋‚ณ๋Š” ๊ฑฐ์œ„๋กœ ์ธ์‹๋˜๋˜ ์ธํ„ฐ๋„ท ๋น„์ฆˆ๋‹ˆ์Šค ๋ถ„์•ผ๋Š” ์ƒˆ๋กœ์šด ๊ตญ๋ฉด์œผ๋กœ ์ ‘์–ด๋“ค๊ณ  ์žˆ๋Š” ์‹ค์ •์ด๋‹ค. ๊ณ ์œ„ํ—˜์„ ๊ฐ์ˆ˜ํ•ด์•ผ ํ•˜๋Š” ๋ฒค์ฒ˜๊ธฐ์—…๋“ค์˜ ํŠน์„ฑ์ƒ ๋‹จ์ง€ 10% ๋ฏธ๋งŒ์˜ ๋ฒค์ฒ˜๊ธฐ์—…๋“ค๋งŒ์ด ์„ฑ๊ณต์ ์ธ ๊ธฐ์—…์œผ๋กœ ์„ฑ์žฅํ•˜๊ณ  ์žˆ๋Š” ํ˜„์‹ค ์†์—์„œ, ๋„ˆ๋ฌด๋‚˜ ๋งŽ์€ ๋ฒค์ฒ˜๊ธฐ์—…๋“ค์˜ ์šฐํ›„์ฃฝ์ˆœ(้›จๅพŒ็ซน็ญ)์‹์˜ ๊ธฐ์—… ์„ค๋ฆฝ์€ ์ง„์ •ํ•œ ๋ฒค์ฒ˜๊ธฐ์—…์˜ ์ทจ์ง€์™€ ๋ชฉ์ ์„ ๋ฌด์ƒ‰์ผ€ ํ•˜๋ฉฐ, ๊ฑด์ „ํ•œ ๋ฒค์ฒ˜๊ธฐ์—…์˜ ์„ ๋ณ„์—๋„ ์•…์˜ํ–ฅ์„ ๋ฏธ์น˜๊ณ  ์žˆ๋‹ค

    P-Cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies

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    BACKGROUND: Proteinuria is a cardinal feature of glomerular disease, including diabetic nephropathy, and the glomerular filtration barrier acts as a filter, restricting protein excretion in urine. We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by diabetes in vivo and by high glucose in vitro. METHODS: In vivo, 24 Sprague-Dawley rats were injected with diluent [control (C), n=8] or streptozotocin intraperitoneally and the latter were left untreated (DM, n=8) or treated with insulin (DM+I, n=8) for 6 weeks. In vitro, immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+19.4 mM mannitol (LG+M) or 25 mM glucose (HG) with or without protein kinase C (PKC) inhibitor (10(-7) M calphostin C or 10(-6) M GF 109203X). Reverse transcription-polymerase chain reaction, western blotting for P-cadherin mRNA and protein expression, respectively, were performed with sieved glomeruli and cell lysates, and immunofluorescence staining was undertaken with renal tissue. RESULTS: Twenty-four hour urinary albumin excretion was significantly higher in DM compared with C and DM+I rats (P<0.05). Glomerular P-cadherin mRNA expression was significantly lower in DM (1.36+/-0.20x10(-2) attm/ng RNA) than in C rats (2.61+/-0.33x10(-2) attm/ng RNA) (P<0.05). P-Cadherin protein expression, assessed by western blot and immunofluorescence staining, was also decreased in DM compared with C and DM+I glomeruli. HG significantly reduced P-cadherin mRNA and protein expression in cultured podocytes by 42% and 62%, respectively (P<0.05), and these decrements were ameliorated by PKC inhibitor. CONCLUSIONS: Diabetes in vivo and exposure of podocytes to HG in vitro reduced P-cadherin mRNA and protein expression, and PKC was involved in the regulation of HG-induced down-regulation of P-cadherin. These findings suggest that the decrease in P-cadherin expression is connected with the early changes of diabetic nephropathy and, thus, may contribute to the development of proteinuria.ope

    Differential Gene Expression According to the Size ofGlomeruli in Experimental Diabetic Nephropathy

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    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.ope

    ์ฃผ์„์ด ํ•จ์œ ๋œ ํŒฝ์ฐฝํ‘์—ฐ์˜ ์ œ์กฐ์™€ ๋ฆฌํŠฌ ์ด์ฐจ ์ „์ง€์šฉ ์Œ๊ทน์žฌ๋ฃŒ๋กœ์„œ์˜ ํŠน์„ฑ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :ํ™”ํ•™์ƒ๋ฌผ๊ณตํ•™๋ถ€,2006.Maste

    (The) effect of high glucose and cyclosporine A on apoptosis in cultured podocytes

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    ์˜๊ณผํ•™๊ณผ/์„์‚ฌ[ํ•œ๊ธ€]์‹ธ์ดํด๋กœ์Šคํฌ๋ฆฐ (CsA)์€ ์‹ ์ด์‹ ํ›„ ์‚ฌ์šฉํ•˜๋Š” ๊ฐ•๋ ฅํ•œ ๋ฉด์—ญ์–ต์ œ์ œ๋กœ ์ด์‹์‹  ์ƒ์กด์œจ์„ ์œ ์˜ํ•˜๊ฒŒ ํ˜ธ์ „์‹œ์ผฐ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ CsA์„ ์žฅ๊ธฐ๊ฐ„ ์‚ฌ์šฉํ•  ๊ฒฝ์šฐ ๊ตฌ์‹ฌ์„ฑ ์‹ ์†Œ๋™๋งฅ ๋ณ‘๋ณ€, ์„ธ๋‡จ๊ด€ ์œ„์ถ•, ์„ธ๋‡จ๊ด€-๊ฐ„์งˆ์„ฑ ์„ฌ์œ ํ™”, ๊ทธ๋ฆฌ๊ณ  ์‚ฌ๊ตฌ์ฒด๊ฒฝํ™”์ฆ ๋“ฑ์ด ๋™๋ฐ˜๋˜๋Š” ๋งŒ์„ฑ CsA ์‹ ๋…์„ฑ์ด ๋ฐœ์ƒํ•˜๊ฒŒ ๋˜๋Š”๋ฐ, ์ด๋Ÿฌํ•œ ๋งŒ์„ฑ CsA ์‹ ๋…์„ฑ์˜ ๋ณ‘์ธ์œผ๋กœ๋Š” ๊ตฌ์‹ฌ์„ฑ ์„ธ๋™๋งฅ์˜ ์ˆ˜์ถ•์œผ๋กœ ์ธํ•œ ํ—ˆํ˜ˆ๊ณผ ์„ธํฌ์‚ฌ๋ฉธ ๋“ฑ์ด ์žˆ๋‹ค. ๋˜ํ•œ, ์„ธํฌ์‚ฌ๋ฉธ์€ ๋‹น๋‡จ๋ณ‘์„ฑ ์‹ ๋ณ‘์ฆ์˜ ํŠน์ง• ์ค‘ ํ•˜๋‚˜์ธ ์กฑ์„ธํฌ ์ˆ˜์˜ ๊ฐ์†Œ์™€๋„ ๋ฐ€์ ‘ํ•˜๊ฒŒ ๊ด€๋ จ๋˜์–ด ์žˆ๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค. ๋‹น๋‡จ๋ณ‘์„ฑ ์‹ ๋ณ‘์ฆ์€ ์ „ ์„ธ๊ณ„์ ์œผ๋กœ ๋ง๊ธฐ ์‹ ๋ถ€์ „์ฆ์˜ ๊ฐ€์žฅ ํ”ํ•œ ์›์ธ ์งˆํ™˜์œผ๋กœ, ๋‹น๋‡จ๋ณ‘์„ฑ ์‹ ๋ณ‘์ฆ์— ์˜ํ•œ ๋ง๊ธฐ ์‹ ๋ถ€์ „์ฆ ํ™˜์ž์˜ ์ฆ๊ฐ€์™€ ํ•จ๊ป˜ ์‹ ์ด์‹์„ ๋ฐ›๋Š” ๋‹น๋‡จ๋ณ‘ ํ™˜์ž๋„ ๋”์šฑ ์ฆ๊ฐ€ํ•  ๊ฒƒ์œผ๋กœ ์˜ˆ์ƒ๋œ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋‹น๋‡จ๋ณ‘์„ ๋™๋ฐ˜ํ•œ ๋ง๊ธฐ ์‹ ๋ถ€์ „์ฆ ํ™˜์ž์—์„œ์˜ ์ด์‹ ํ›„ ์‹ ์ƒ์กด์œจ์€ ๊ฐ์—ผ์ด๋‚˜ ๊ธ‰์„ฑ ๊ฑฐ๋ถ€๋ฐ˜์‘์œผ๋กœ ์ธํ•˜์—ฌ ๋น„๋‹น๋‡จ๋ณ‘ ๋ง๊ธฐ ์‹ ๋ถ€์ „์ฆ ํ™˜์ž์— ๋น„ํ•˜์—ฌ ๋‚ฎ์€ ๊ฒƒ์œผ๋กœ ๋ณด๊ณ ๋˜๊ณ  ์žˆ๋‹ค.์ด์— ๋ณธ ์—ฐ๊ตฌ์ž๋Š” ๋‹น๋‡จ๋ณ‘ ์‹ ์ด์‹ ํ™˜์ž์—์„œ์˜ ๋‚ฎ์€ ์‹ ์ƒ์กด์œจ๊ณผ ์กฑ์„ธํฌ ์‚ฌ๋ฉธ ์‚ฌ์ด์˜ ์—ฐ๊ด€์„ฑ์„ ๊ทœ๋ช…ํ•˜๊ธฐ ์œ„ํ•˜์—ฌ ๊ณ ํฌ๋„๋‹น๊ณผ CsA์œผ๋กœ ์ž๊ทนํ•œ ์กฑ์„ธํฌ์—์„œ์˜ ์„ธํฌ์‚ฌ๋ฉธ์„ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค. ์กฑ์„ธํฌ๋ฅผ 33๏ผŸ์—์„œ ๊ฐ๋งˆ์ธํ„ฐํŽ˜๋ก ์ด ํฌํ•จ๋œ ๋ฐฐ์–‘์•ก์œผ๋กœ ๊ณ„๋Œ€ ๋ฐฐ์–‘ํ•˜์˜€์œผ๋ฉฐ, ์ดํ›„ 37๏ผŸ์—์„œ ๊ฐ๋งˆ์ธํ„ฐํŽ˜๋ก ์ด ์—†๋Š” ๋ฐฐ์–‘์•ก์œผ๋กœ ๋ฐฐ์–‘ํ•˜๋ฉด์„œ ๋ถ„ํ™”๋ฅผ ์‹œ์ผฐ๋‹ค. ์กฑ์„ธํฌ์˜ ๋ถ„ํ™”๋ฅผ ํ™•์ธํ•œ ํ›„ ์šฐํƒœ์•„ํ˜ˆ์ฒญ์ด ์—†๋Š” ๋ฐฐ์–‘์•ก์œผ๋กœ 24์‹œ๊ฐ„ ๋™์•ˆ ๋ฐฐ์–‘ํ•œ ๋‹ค์Œ, 5.6 mM ํฌ๋„๋‹น (NG), NG + 24.4 mM ๋งŒ๋‹ˆํ†จ (NG + M), NG + 10-6 M CsA (NG + CsA), 30 mM ํฌ๋„๋‹น (HG), ๊ทธ๋ฆฌ๊ณ  HG + 10-6 M CsA (HG + CsA) ๋ฐฐ์–‘์•ก์œผ๋กœ 72์‹œ๊ฐ„ ๋™์•ˆ ๋ฐฐ์–‘ํ•˜์˜€๋‹ค. mRNA ๋ฐœํ˜„์€ RT-PCR๋กœ, ๋‹จ๋ฐฑ ๋ฐœํ˜„์€ Western blot๋กœ, ๊ทธ๋ฆฌ๊ณ  ์„ธํฌ์‚ฌ๋ฉธ์€ Hoechst 33258 ์—ผ์ƒ‰๊ณผ FACS๋ฅผ ์ด์šฉํ•˜์—ฌ ๋ถ„์„ํ•˜์—ฌ ๋‹ค์Œ๊ณผ ๊ฐ™์€ ๊ฒฐ๊ณผ๋ฅผ ์–ป์—ˆ๋‹ค.1. ์กฑ์„ธํฌ์—์„œ Bax/Bcl-2 mRNA ๋ฐœํ˜„๋น„๋Š” NG + CsA๊ตฐ๊ณผ HG + CsA๊ตฐ์—์„œ NG๊ตฐ์— ๋น„ํ•˜์—ฌ ๊ฐ๊ฐ 3๋ฐฐ, 2.8๋ฐฐ ์ฆ๊ฐ€๋˜์—ˆ์œผ๋ฉฐ (p<0.05), Bax/Bcl-2์˜ ๋‹จ๋ฐฑ ๋ฐœํ˜„๋น„๋„ NG๊ตฐ์— ๋น„ํ•˜์—ฌ NG + CsA๊ตฐ๊ณผ HG + CsA๊ตฐ์—์„œ 2.2๋ฐฐ, 1.7๋ฐฐ ์ฆ๊ฐ€๋˜์—ˆ๋‹ค (p<0.01). ๊ทธ๋Ÿฌ๋‚˜ ๊ณ ํฌ๋„๋‹น์ด๋‚˜ ๋งŒ๋‹ˆํ†จ์€ ์กฑ์„ธํฌ์˜ Bax์™€ Bcl-2 mRNA ๋ฐ ๋‹จ๋ฐฑ ๋ฐœํ˜„์— ์˜ํ–ฅ์„ ๋ฏธ์น˜์ง€ ์•Š์•˜๋‹ค.2. TGF-๏ผŸ] mRNA ๋ฐ ๋‹จ๋ฐฑ ๋ฐœํ˜„์€ NG๊ตฐ๊ณผ HG๊ตฐ์— ๋น„ํ•˜์—ฌ NG + CsA๊ตฐ๊ณผ HG + CsA๊ตฐ์—์„œ ์˜์˜์žˆ๊ฒŒ ์ฆ๊ฐ€๋˜์—ˆ๋‹ค (p<0.05). ๊ทธ๋Ÿฌ๋‚˜ ๊ณ ํฌ๋„๋‹น์ด๋‚˜ ๋งŒ๋‹ˆํ†จ์€ ์กฑ์„ธํฌ์˜ TGF-๏ผŸ] ๋ฐœํ˜„์— ์˜ํ–ฅ์„ ๋ฏธ์น˜์ง€ ์•Š์•˜๋‹ค.3. Hoechst 33258 ์—ผ์ƒ‰์— ์˜ํ•œ apoptotic cell์˜ ์ˆ˜๋Š” CsA ์ฒ˜์น˜๊ตฐ์—์„œ ์˜์˜์žˆ๊ฒŒ ์ฆ๊ฐ€๋˜์—ˆ์œผ๋ฉฐ, FACS ๋ถ„์„์ƒ์œผ๋กœ๋„ CsA ์ฒ˜์น˜๊ตฐ์—์„œ apoptotic cell์˜ ๋น„์œจ์ด ์œ ์˜ํ•˜๊ฒŒ ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค (p<0.01).์ด์ƒ์˜ ๊ฒฐ๊ณผ๋กœ ์กฑ์„ธํฌ์—์„œ ์‹ธ์ดํด๋กœ์Šคํฌ๋ฆฐ์ด ์„ธํฌ์‚ฌ๋ฉธ์„ ์ฆ๊ฐ€์‹œ์ผฐ์œผ๋ฉฐ, ์‹ธ์ดํด๋กœ์Šคํฌ๋ฆฐ์— ์˜ํ•œ ์„ธํฌ์‚ฌ๋ฉธ์ด ๊ณ ํฌ๋„๋‹น ์กฐ๊ฑด ํ•˜์—์„œ ๋” ์‹ฌํ™”๋˜์ง€๋Š” ์•Š์„ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. [์˜๋ฌธ]Cyclosporine A (CsA) is a potent immunosuppressant for transplantation and various autoimmune diseases, and has markedly improved the success of organ transplantation. However, the major limiting problem in the long-term use of CsA is chronic nephrotoxicity, a histologic lesion characterized by affterent arteriolopathy, tubular atrophy, tubulointerstitial fibrosis, and finally glomerulosclerosis. The pathogenesis of chronic CsA nephrotoxicity is not fully understood, but several previous studies have suggested that it is attributed to sustained ischemia and apoptosis of tubular cells, mesangial cells, and podocytes. On the other hand, apoptosis of podocytes is also considered one of the pathophysiologic events in diabetic nephropathy, resulting in decrease in podocytes number. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in many countries, so more diabetic ESRD patients are supposed to receive a kidney transplant. However, the renal survival rates in diabetic ESRD patients are known to be worse than non-diabetic ESRD patients due to more infection and acute rejection, in which apoptosis is known to be implicated.In this study, we evaluated the combined effect of high glucose and CsA on apoptosis in cultured podocytes to determine whether high glucose and CsA exert synergistic deleterious effects on podocytes, leading to poor renal survival in diabetic transplant patients in clinical field. Conditionally immortalized mouse podocytes were cultured under permissive conditions at 33๏ผŸ with ๏ผŸ-interferon and were subcultured, and then allowed to differentiate at 37๏ผŸ without ๏ผŸ-interferon. After confirming differentiation of podocytes and serum restriction for 24 hours, podocytes were exposed to medium containing 5.6 mM glucose (NG), NG + 24.4 mM mannitol (NG + M), NG + 10-6 M CsA (NG + CsA), 30 mM glucose (HG), or HG + 10-6 M CsA (HG + CsA) for 72 hours. mRNA expression was determined by RT-PCR, protein expression by Western blot, and apoptosis by Hoechst 33258 staining and FACS analysis. The results were as follows;1. Bax/Bcl-2 mRNA expression ratio was significantly increased in NG + CsA and HG + CsA cells by 3.0- and 2.8-fold, respectively, compared to podocytes exposed to NG medium (p<0.05). Bax/Bcl-2 protein ratio was also significantly increased in NG + CsA and HG + CsA cells by 2.2- and 1.7-fold, respectively, compared to NG podocytes (p<0.01). However high glucose and mannitol had no effect on Bax and Bcl-2 mRNA and protein expression.2. TGF-๏ผŸ] mRNA and protein expression were significantly higher in NG + CsA and HG + CsA podocytes than NG cells (p<0.05). However high glucose and mannitol had no effect on TGF-๏ผŸ] expression.3. The numbers of apoptotic cell determined by Hoechst 33258 staining were significantly increased by CsA treatment, and FACS analysis also revealed significantly higher proportion of apoptotic cells in CsA-treated groups.In conclusion, these results suggest that CsA increases apoptosis in podocytes and diabetes status may not affect CsA-induced apoptosis of podocytes.ope

    ์žก๊ฒฌ์—์„œ ์ƒˆ๋กœ์šด ํ•ญํ˜ˆ์ „ํ˜ˆ์•ก์ ‘์ด‰ํ‘œ๋ฉด ์ฝ”ํŒ… ์ธ์กฐํ˜ˆ๊ด€์˜ ํ˜ˆ์•ก์ ํ•ฉ์„ฑ ๋ถ„์„

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜ํ•™๊ณผ ํ‰๋ถ€์™ธ๊ณผํ•™,2001.Maste

    ์„œ์šธ์‹œ ๋‚ด๋ถ€์‹œ๊ฐ€์ง€ ์žฌํ™œ์„ฑํ™”๋ฅผ ์œ„ํ•œ ๊ณ„ํš : ์„œ์šธ์‹œ ๋™๋Œ€๋ฌธ๊ตฌ ์šฉ๋‘1๋™์„ ์ค‘์‹ฌ์œผ๋กœ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ํ™˜๊ฒฝ๋Œ€ํ•™์› :ํ™˜๊ฒฝ์กฐ๊ฒฝํ•™๊ณผ ๋„์‹œ์„ค๊ณ„์ „๊ณต,2000.Maste
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