Terada Naomi, Karim Mohammad Rabiul, Izawa Takeshi, Kuwamura Mitsuru, Yamate Jyoji
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.
Clin Exp Nephrol. 2018 Dec;22(6):1240-1250. doi: 10.1007/s10157-018-1583-1. Epub 2018 May 26.
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.
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.
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.
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.
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。
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。
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。
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。