Chronic Hematuria Increases Chronic Kidney Injury and Epithelial-Mesenchymal Transition in 5/6 Nephrectomy Rats.
Chronic Hematuria Increases Chronic Kidney Injury and Epithelial-Mesenchymal Transition in 5/6 Nephrectomy Rats.
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DOI：
10.3389/fmed.2021.753506
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发表时间：
2021
影响因子：
3.9
通讯作者：
Brodsky SV
中科院分区：
文献类型：
--
作者：
Xiao M;Medipally AK;Biederman L;Satoskar AA;Ivanov I;Rovin BH;Brodsky SV
慢性肾脏疾病（CKD）是许多肾脏疾病的常见结果。间质纤维化和小管萎缩（IFTA）是CKD的组织学标志。血尿是许多人类肾脏疾病的常见症状。游离血红蛋白可通过产生活性氧（ROS）影响小管上皮细胞。小管上皮细胞的上皮-间质转化（EMT）已被证明在IFTA的发展中起重要作用。本研究的目的是确定慢性血尿对5/6肾切除（5/6NE）大鼠CKD模型的CKD进展的影响。5/6只NE大鼠分别口服华法林（0.5 mg/kg/d）或对照组。监测动物26周，每周测定凝血酶原时间（PT）、血清肌酐（SCr）和血尿。对残肾进行铁、三色和EMT（波形蛋白、e -钙粘蛋白、平滑肌肌动蛋白）标记染色。研究结束时，采用蛋白羰基法和血红素加氧酶1 （HMOX1）免疫组化检测肾脏ROS。TUNEL法检测细胞凋亡。华法林治疗导致PT比对照组增加1.5-2.5倍，血尿和SCr增加。组织学上，与对照组相比，华法林治疗的动物有更多的铁阳性小管上皮细胞和IFTA增加（42.9±17% vs. 18.3±2.6%）。华法林治疗大鼠肾脏ROS升高。与对照的5/6NE大鼠相比，华法林治疗的5/6NE显示EMT证据的小管数量显着增加。华法林处理的5/6 NE大鼠小管上皮细胞凋亡数量较高。慢性血尿导致CKD大鼠铁阳性小管上皮细胞、EMT、细胞凋亡增加，IFTA更突出。我们的数据表明慢性血尿在CKD的进展中起重要作用。
Chronic kidney disease (CKD) is a common outcome of many kidney diseases. Interstitial fibrosis and tubular atrophy (IFTA) is a histologic hallmark of CKD. Hematuria is a common symptom in many human kidney diseases. Free hemoglobin may affect tubular epithelial cells by generating reactive oxygen species (ROS). Epithelial–mesenchymal transition (EMT) of the tubular epithelial cells has been shown to play an important role in the IFTA development. The aim of this study was to determine the effects of chronic hematuria on the CKD progression in 5/6 nephrectomy (5/6NE) rat model of CKD. 5/6 NE rats were treated with oral warfarin (0.5 mg/kg/day) or vehicle (control). The animals were monitored for 26 weeks, while prothrombin time (PT), serum creatinine (SCr), and hematuria were measured weekly. Staining for iron, trichrome, and EMT (vimentin, E-cadherin, smooth muscle actin) markers was performed on the remnant kidneys. ROS were detected in the kidneys by protein carbonyl assay and immunohistochemistry for heme oxygenase 1 (HMOX1), at the end of the study. Apoptosis was detected by TUNEL assay. Warfarin treatment resulted in a PT increase 1.5–2.5 times from control and an increase in hematuria and SCr. Histologically, warfarin-treated animals had more iron-positive tubular epithelial cells and increased IFTA as compared to control (42.9 ± 17% vs. 18.3 ± 2.6%). ROS were increased in the kidney in warfarin-treated rats. The number of tubules that show evidence of EMT was significantly higher in warfarin-treated 5/6NE as compared to control 5/6NE rats. The number of apoptotic tubular epithelial cells was higher in warfarin-treated 5/6 NE rats. Chronic hematuria results in increased iron-positive tubular epithelial cells, EMT, apoptosis, and more prominent IFTA in CKD rats. Our data suggest an important role of chronic hematuria in the progression of CKD.
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影响因子：
3.2
作者：
Farris AB;Colvin RB
通讯作者：
Colvin RB
影响因子：
8.8
作者：
Rostaing, L.;Hertig, A.;Rondeau, E.
通讯作者：
Rondeau, E.
影响因子：
4.2
作者：
Ozcan, A.;Ware, K.;Brodsky, S. V.
通讯作者：
Brodsky, S. V.
影响因子：
7.4
作者：
Denamur, Sophie;Tyteca, Donatienne;Mingeot-Leclercq, Marie-Paule
通讯作者：
Mingeot-Leclercq, Marie-Paule
DOI：
10.1097/01.asn.0000077411.98742.54
发表时间：
2003-08-01
影响因子：
13.6
作者：
Ha, H;Lee, HB
通讯作者：
Lee, HB