Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected Caco-2 cells
Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected Caco-2 cells
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金雀异黄素抑制轮状病毒复制并上调轮状病毒感染的 Caco-2 细胞中 AQP4 的表达
DOI：
10.1007/s00705-015-2404-4
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发表时间：
2015-06-01
影响因子：
2.7
通讯作者：
Zhao, Wenchang
中科院分区：
文献类型：
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作者：
Huang, Haohai;Liao, Dan;Zhao, Wenchang
轮状病毒（RV）是婴幼儿严重脱水性胃肠炎和急性腹泻病的主要病因。已有研究表明染料木黄酮能抑制有包膜或无包膜病毒的感染性。虽然染料木黄酮的生物学特性已被充分研究，但其抗轮状病毒特性的作用机制尚未完全阐明。在这里，我们报告，染料木素显着抑制RV-Wa replicationin体外抑制病毒RNA转录，并可能病毒蛋白质的合成。有趣的是，我们还发现，水通道蛋白4（AQP 4）的mRNA和蛋白质的表达，这是下调RV感染的Caco-2细胞，可以上调染料木素在时间和剂量依赖性的方式。进一步的实验证实，染料木黄酮通过PKA激活触发CREB磷酸化，随后促进AQP 4基因转录。这些结果表明，RV感染的病理生理机制涉及AQP 4的表达减少，染料木素可能是一个有用的候选人，通过抑制轮状病毒复制和上调AQP 4表达通过cAMP/PKA/CREB信号通路，开发一种新的抗RV策略。金雀异黄素对RV引起的腹泻的作用有待进一步研究。
Rotavirus (RV) is the primary cause of severe dehydrating gastroenteritis and acute diarrheal disease in infants and young children. Previous studies have revealed that genistein can inhibit the infectivity of enveloped or nonenveloped viruses. Although the biological properties of genistein are well studied, the mechanisms of action underlying their anti-rotavirus properties have not been fully elucidated. Here, we report that genistein significantly inhibits RV-Wa replicationin vitroby repressing viral RNA transcripts, and possibly viral protein synthesis. Interestingly, we also found that aquaporin 4 (AQP4) mRNA and protein expression, which was downregulated in RV-infected Caco-2 cells, can be upregulated by genistein in a time- and dose-dependent manner. Further experiments confirmed that genistein triggers CREB phosphorylation through PKA activation and subsequently promotes AQP4 gene transcription. These findings suggest that the pathophysiological mechanism of RV infection involves decreased expression of AQP4 and that genistein may be a useful candidate for developing a new anti-RV strategy by inhibiting rotavirus replication and upregulating AQP4 expression via the cAMP/PKA/CREB signaling pathway. Further studies on the effect of genistein on RV-induced diarrhea are warranted.