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β-连环蛋白在顺铂诱导的大鼠肾衰竭再生肾小管中的表达

Expression of β-catenin in regenerating renal tubules of cisplatin-induced kidney failure in rats.

作者信息

Terada Naomi, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji

机构信息

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano City, Osaka, 598-8531, Japan.

出版信息

Clin Exp Nephrol. 2018 Dec;22(6):1240-1250. doi: 10.1007/s10157-018-1583-1. Epub 2018 May 26.

Abstract

BACKGROUND

β-Catenin is a multi-functional protein involved in nephrogenesis and also plays important roles in renal injury. Here, the expression of β-catenin was investigated in the proximal renal tubular epithelial cells in cisplatin (CDDP)-induced acute kidney injury (AKI) and chronic kidney injury (CKI), because CDDP-induced renal lesions were characterized by proximal renal tubular epithelial degeneration/regeneration and subsequent interstitial fibrosis.

METHODS

F344 rats were treated with CDDP. The expression of β-catenin and proliferative (Ki67) or fibrogenic [vimentin, α-smooth action (α-SMA)] markers was analyzed by immunolabeling.

RESULTS

β-Catenin, vimentin and Ki67 were not seen in the proximal renal tubules of control rats. Interestingly, in CDDP-induced AKI, the regenerating proximal renal tubular epithelial cells reacting strongly with Ki67 expressed membranous or cytoplasmic β-catenin and also showed a positive reaction to vimentin but not to α-SMA. In CDDP-induced CKI, the epithelial cells of abnormally dilated or atrophied renal tubules did not react to β-catenin or Ki67, but showed positive reactions to vimentin and α-SMA. β-Catenin mRNAs were significantly increased in AKI and significantly decreased in CKI.

CONCLUSION

Newly expressed β-catenin in the proximal renal tubules after AKI may participate in functional regeneration. In CKI, epithelial cells of abnormal renal tubules did not express β-catenin but reacted to vimentin, and α-SMA might indicate the epithelial-mesenchymal transition (EMT) formation, because α-SMA is usually expressed in myofibroblasts forming via EMT. The presence or absence of β-catenin expression would become a marker for the EMT phenomenon in progressive renal fibrosis.

摘要

背景

β-连环蛋白是一种多功能蛋白,参与肾发生,在肾损伤中也发挥重要作用。在此,研究了β-连环蛋白在顺铂(CDDP)诱导的急性肾损伤(AKI)和慢性肾损伤(CKI)的近端肾小管上皮细胞中的表达,因为CDDP诱导的肾损伤的特征是近端肾小管上皮变性/再生以及随后的间质纤维化。

方法

用CDDP处理F344大鼠。通过免疫标记分析β-连环蛋白和增殖(Ki67)或纤维化[波形蛋白、α-平滑肌肌动蛋白(α-SMA)]标志物的表达。

结果

在对照大鼠的近端肾小管中未观察到β-连环蛋白、波形蛋白和Ki67。有趣的是,在CDDP诱导的AKI中,与Ki67强烈反应的再生近端肾小管上皮细胞表达膜性或细胞质β-连环蛋白,并且对波形蛋白呈阳性反应,但对α-SMA无反应。在CDDP诱导的CKI中,异常扩张或萎缩的肾小管上皮细胞对β-连环蛋白或Ki67无反应,但对波形蛋白和α-SMA呈阳性反应。β-连环蛋白mRNA在AKI中显著增加,在CKI中显著降低。

结论

AKI后近端肾小管中新表达的β-连环蛋白可能参与功能再生。在CKI中,异常肾小管的上皮细胞不表达β-连环蛋白,但对波形蛋白有反应,并且α-SMA可能表明上皮-间质转化(EMT)的形成,因为α-SMA通常在通过EMT形成的肌成纤维细胞中表达。β-连环蛋白表达的有无将成为进行性肾纤维化中EMT现象的标志物。

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