Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.
Department of Anesthesiology, Guanyun County People's Hospital, Lianyungang, Jiangsu 222200, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8891-8899. doi: 10.3892/mmr.2017.7728. Epub 2017 Oct 5.
The implications of epithelial‑mesenchymal transdifferentiation (EMT) have extended beyond the confines of renal fibrosis to renal tubulointerstitial fibrosis. It has been proposed that EMT may be one of the mechanisms involved in the pathogenesis of renal fibrosis. However, the underlying mechanisms remain unknown. Transforming growth factor (TGF)‑β1 is considered to be an important cytokine which regulates the transdifferentiation of tubular epithelial cells into myofibroblasts in renal tubulointerstitial fibrosis. In the present study, normal rat kidney tubular epithelial cells (NRK‑52E) were treated for 48 h with TGF‑β1 (5 ng/ml) and different concentrations of artesunate (ART; 0.01, 0.1 and 1 µg/ml). Western blotting, reverse transcription‑semi quantitative polymerase chain reaction analysis and immunofluorescence staining were used to evaluate the expression of bone morphogenetic protein (BMP)‑7, uterine sensitization‑associated gene (USAG)‑1, E‑cadherin, α‑smooth muscle actin (α‑SMA) and extracellular matrix collagen type I (Col I) mRNA. ART was able to attenuate renal injury in a unilateral ureteral obstruction model. However, its anti‑fibrotic effect remains to be elucidated. In the present study, it was observed that ART was able to ameliorate the TGF‑β1‑induced alterations in cellular morphology. In addition, ART inhibited the TGF‑β1‑induced USAG‑1 increase and the decrease in BMP‑7. Treatment with ART markedly attenuated the TGF‑β1‑induced upregulation of α‑SMA and downregulation of E‑cadherin. Additionally, ART was able to significantly attenuate the deposition of interstitial collagens, including Col I. The results of the present study further verified the therapeutic efficacy of ART in TGF‑β1‑induced renal interstitial fibrosis. These findings indicated that ART may hold the potential to prevent chronic kidney diseases via the suppression of USAG‑1 expression or by increasing BMP‑7 expression.
上皮-间充质转化（EMT）的意义已经超出了肾纤维化的范围，延伸到了肾小管间质纤维化。有人提出 EMT 可能是肾纤维化发病机制中的一个机制。然而，其潜在机制尚不清楚。转化生长因子（TGF）-β1 被认为是一种重要的细胞因子，可调节肾小管上皮细胞向肾间质成纤维细胞的转化。在本研究中，用 TGF-β1（5ng/ml）和不同浓度的青蒿琥酯（ART；0.01、0.1 和 1μg/ml）处理正常大鼠肾近端小管上皮细胞（NRK-52E）48h。采用 Western blot、逆转录-半定量聚合酶链反应分析和免疫荧光染色检测骨形态发生蛋白（BMP）-7、子宫致敏相关基因（USAG）-1、E-钙黏蛋白、α-平滑肌肌动蛋白（α-SMA）和细胞外基质胶原 I（Col I）mRNA 的表达。ART 能够减轻单侧输尿管梗阻模型中的肾损伤。然而，其抗纤维化作用仍有待阐明。在本研究中，观察到 ART 能够改善 TGF-β1 诱导的细胞形态改变。此外，ART 抑制 TGF-β1 诱导的 USAG-1 增加和 BMP-7 减少。ART 治疗显著减弱了 TGF-β1 诱导的 α-SMA 上调和 E-钙黏蛋白下调。此外，ART 能够显著减轻间质胶原的沉积，包括 Col I。本研究的结果进一步验证了 ART 在 TGF-β1 诱导的肾间质纤维化中的治疗效果。这些发现表明，ART 可能通过抑制 USAG-1 表达或增加 BMP-7 表达来预防慢性肾脏疾病。
