National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
Virol J. 2011 Sep 8;8:431. doi: 10.1186/1743-422X-8-431.
Hepatitis C virus (HCV) is a major health problem in developing countries including Pakistan. Chronic HCV infection results in progressive liver disease including fibrosis, cirrhosis, insulin resistance and eventually hepatocellular carcinoma (HCC). Ionotrophic purinergic (P2X) receptors are identified to involve in a spectrum of physiological and pathophysiological processes. However, the role of P2X receptors in HCV liver associated diseases still remains to be investigated. The current study was designed to identify the presence of P2X receptors in human liver cells. Furthermore, it investigates the response of P2X receptors towards HCV structural proteins (E1E2). To determine that how many isoforms of P2X receptors are expressed in human liver cells, human hepatoma cell line (Huh-7) was used. Transcripts (mRNA) of five different isoforms of P2X receptors were identified in Huh-7 cells. To examine the gene expression of identified isoforms of P2X receptors in presence of HCV structural proteins E1E2, Huh-7/E1E2 cell line (stably expressing HCV structural proteins E1E2) was used. The results showed significant increase (6.2 fold) in gene expression of P2X4 receptors in Huh-7/E1E2 cells as compared to control Huh-7 cells. The findings of present study confirmed the presence of transcripts of five different isoforms of P2X receptors in human liver cells and suggest that P2X4 receptors could be represented an important component of the purinergic signaling complex in HCV induced liver pathogenesis.
丙型肝炎病毒 (HCV) 是包括巴基斯坦在内的发展中国家的一个主要健康问题。慢性 HCV 感染会导致进行性肝脏疾病，包括纤维化、肝硬化、胰岛素抵抗，最终导致肝细胞癌 (HCC)。离子型嘌呤能 (P2X) 受体被确定参与一系列生理和病理生理过程。然而，P2X 受体在 HCV 相关肝病中的作用仍有待研究。本研究旨在确定 P2X 受体在人肝细胞中的存在。此外，它还研究了 P2X 受体对 HCV 结构蛋白 (E1E2) 的反应。为了确定 P2X 受体在人肝细胞中表达的亚型有多少，使用了人肝癌细胞系 (Huh-7)。在 Huh-7 细胞中鉴定出五种不同亚型的 P2X 受体的转录本 (mRNA)。为了研究在 HCV 结构蛋白 E1E2 存在下鉴定出的 P2X 受体亚型的基因表达，使用了 Huh-7/E1E2 细胞系（稳定表达 HCV 结构蛋白 E1E2）。结果显示，与对照 Huh-7 细胞相比，Huh-7/E1E2 细胞中 P2X4 受体的基因表达显著增加 (6.2 倍)。本研究的结果证实了人肝细胞中存在五种不同亚型的 P2X 受体的转录本，并表明 P2X4 受体可能是 HCV 诱导的肝发病机制中嘌呤能信号复合物的重要组成部分。
