Sertraline Reduces Albuminuria by Interfering with Caveolae-Mediated Endocytosis through Glomerular Endothelial and Epithelial Cells
Sertraline Reduces Albuminuria by Interfering with Caveolae-Mediated Endocytosis through Glomerular Endothelial and Epithelial Cells
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舍曲林通过干扰肾小球内皮细胞和上皮细胞小凹介导的内吞作用来减少蛋白尿
DOI：
10.1159/000503917
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发表时间：
2019
影响因子：
4.2
通讯作者：
Nitta Kosaku
中科院分区：
文献类型：
--
作者：
Moriyama Takahito;Karasawa Kazunori;Hasegawa Fumio;Uchida Keiko;Nitta Kosaku
前言在此之前，我们报道了小窝介导的白蛋白通过肾小球内皮细胞（GEnCs）的细胞内运输途径作为尿白蛋白排泄的一个新的病因学假说。选择性5-羟色胺再摄取抑制剂舍曲林（sertraline，Ser）抑制发动蛋白，发动蛋白在小窝内吞过程中从细胞膜分裂小窝中起关键作用。在这项研究中，我们评估了Ser是否通过干扰白蛋白通过小窝内吞进入GEnCs和足细胞来降低白蛋白尿水平，作为肾小球肾炎的一种新治疗方法。通过免疫荧光（IF）和蛋白质印迹（WB）分析评估白蛋白和小窝蛋白-1（Cav-1）表达水平。白蛋白尿水平测定嘌呤霉素氨基糖苷（PAN）诱导的肾病综合征小鼠模型（PAN小鼠）治疗或不Ser.ResultsIF和WB分析表明，白蛋白的表达水平显着下降，丝氨酸治疗，但是，Cav-1的表达没有减少的基础上，IF结果在GEnCs或足细胞。PAN小鼠无论是否给予Ser，Cav-1表达均增加，足细胞足突消失，GEnCs肿胀。然而，蛋白尿水平并没有增加，在PAN小鼠与丝氨酸治疗相对于正常对照组小鼠（p= 0.17），并观察到一个显着的增加，在PAN小鼠没有Ser治疗（p= 0.0027）。发动蛋白抑制剂可能作为一种新的治疗选择，减少蛋白尿的肾小球肾炎。
IntroductionPreviously, we reported the caveolae-mediated intracellular trafficking pathway of albumin through glomerular endothelial cells (GEnCs) as a new etiological hypothesis of urinary albumin excretion. The selective serotonin reuptake inhibitor, sertraline (Ser), inhibits dynamin, which plays a pivotal role in the fission of caveolae from the cell membrane during caveolae endocytosis.ObjectiveIn this study, we evaluated whether Ser reduces albuminuria levels by interfering with albumin endocytosis through caveolae into GEnCs and podocytes as a novel treatment for glomerulonephritis.MethodsAfter treating the cells with Ser, albumin and caveolin-1 (Cav-1) expression levels were evaluated by immunofluorescence (IF) and western blot (WB) analyses. The albuminuria level was determined by histology in a puromycin aminonucleoside (PAN)-induced nephrotic syndrome mouse model (PAN mice) treated with or without Ser.ResultsIF and WB analyses showed that the albumin expression level was significantly decreased by Ser treatment; however, Cav-1 expression was not decreased in GEnCs or podocytes based on the IF results. In PAN mice treated with or without Ser, Cav-1 expression increased, and the foot process effacement of podocytes and swelling of GEnCs were observed. However, proteinuria levels were not increased in PAN mice treated with Ser relative to that in normal control mice (p= 0.17), and a significant increase was observed in PAN mice without Ser treatment (p= 0.0027).ConclusionsSer interfered with albumin internalization through the caveolae into GEnCs and podocytes and reduced albuminuria. Dynamin inhibitors may serve as a novel therapeutic option for reducing albuminuria in glomerulonephritis.
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影响因子：
3.1
作者：
Saiz-Rodriguez, Miriam;Belmonte, Carmen;Abad-Santos, Francisco
通讯作者：
Abad-Santos, Francisco
DOI：
10.1152/ajprenal.00532.2013
发表时间：
2014-05-01
影响因子：
4.2
作者：
Dobrinskikh, Evgenia;Okamura, Kayo;Blaine, Judith
通讯作者：
Blaine, Judith
不依赖网格蛋白的内吞作用：复杂性不断增加
影响因子：
2.3
作者：
K. Sandvig;Simona Kavaliauskiene;T. Skotland
通讯作者：
T. Skotland
影响因子：
0.7
作者：
Zahed NS;Sharifi M;Karimi M;Nikbakht H
通讯作者：
Nikbakht H
舍曲林抑制动力 GTP 酶活性会抑制动力依赖性内吞作用。
DOI：
--
发表时间：
2010
期刊：
影响因子：
--
作者：
Takahashi;K.;池田裕美子;Kiyofumi Takahashi.
通讯作者：
Kiyofumi Takahashi.