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BAFF signaling drives interstitial transformation of mouse renal tubular epithelial cells in a Pin1-dependent manner
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2021-06-14 , DOI: 10.1007/s11626-021-00598-y
Haiyan Xu 1 , Dan Song 1 , Renfang Xu 1 , Xiaozhou He 1
Affiliation  

Aberrant expression of B cell–activating factor belonging to TNF superfamily (BAFF) and its receptors results in abnormal biological activities in hematopoietic and non-hematopoietic cells and is closely associated with the occurrence and development of various diseases. However, the biological significance and potential mechanisms underlying BAFF signaling in renal tubular epithelial cells (RTECs) remain unknown. This study aimed to investigate the biological role of BAFF signaling in RTECs. Mice primary RTECs were applied. The proliferation status and apoptotic rates were examined by MTS assay and flow cytometry, respectively. The expression of BAFF and its receptors was analyzed via flow cytometry and sodium ion transport function, and cytokeratin-18 expression was detected through immunofluorescence staining. In addition, Pin1 was knocked down via siRNA and its expression was assessed through reverse transcription PCR. Lastly, western blotting was performed to analyze E-cadherin, ɑ-SMA, and Pin1 expression. Results suggested that BAFF-R was significantly upregulated upon IFN-γ stimulation, and enhancement of BAFF signaling promoted cell survival and reduced their apoptotic rate, while simultaneously reducing the epithelial phenotype and promoting the interstitial transformation of cells. Furthermore, Pin1 was significantly increased, along with the upregulation of BAFF signaling in the RTECs, and participated in interstitial transformation induced by BAFF signaling. Collectively, the present results elucidate the potential mechanism of loss of normal function of RTECs under long-term high dose of BAFF stimulation provides a potential therapeutic target for renal interstitial fibrosis, and underlining mechanisms of shortening of long-term outcomes of kidney allografts via augmenting of BAFF signaling.



中文翻译:

BAFF信号以Pin1依赖性方式驱动小鼠肾小管上皮细胞间质转化

TNF超家族(BAFF)及其受体B细胞活化因子的异常表达导致造血和非造血细胞生物学活性异常,与多种疾病的发生发展密切相关。然而,肾小管上皮细胞 (RTEC) 中 BAFF 信号传导的生物学意义和潜在机制仍然未知。本研究旨在研究 BAFF 信号在 RTECs 中的生物学作用。应用了小鼠初级 RTEC。分别通过MTS测定和流式细胞术检查增殖状态和凋亡率。流式细胞仪和钠离子转运功能分析BAFF及其受体的表达,免疫荧光染色检测细胞角蛋白18的表达。此外,通过 siRNA 敲低 Pin1,并通过逆转录 PCR 评估其表达。最后,进行蛋白质印迹以分析 E-cadherin、ɑ-SMA 和 Pin1 的表达。结果表明,在 IFN-γ 刺激下,BAFF-R 显着上调,增强 BAFF 信号传导可促进细胞存活并降低其凋亡率,同时降低上皮表型并促进细胞间质转化。此外,随着 RTEC 中 BAFF 信号的上调,Pin1 显着增加,并参与了 BAFF 信号诱导的间质转化。集体,

更新日期:2021-06-15
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