关键词: ACE2 Liver diseases SARS-CoV-2 TMPRSS2

来  源:   DOI:10.1097/ID9.0000000000000007   PDF(Pubmed)

Abstract:
UNASSIGNED: Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver.
UNASSIGNED: Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People\'s Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines.
UNASSIGNED: The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells.
UNASSIGNED: Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.
摘要:
预先存在的肝病是严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)感染预后较差的危险因素。我们旨在评估慢性乙型肝炎(CHB)和肝细胞癌(HCC)是否会影响肝脏中病毒受体血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的表达。
从浙江大学医学院附属第一医院收集了12对匹配的肝癌和癌旁肝组织。北京大学人民医院收集CHB患者肝活检20例。免疫荧光染色检测ACE2和TMRPSS2的表达,westernblot,和RT-qPCR。在肝细胞系中测试了乙型肝炎病毒(HBV)复制或干扰素对ACE2和TMPRSS2表达的影响。
肝癌组织中TMPRSS2的mRNA表达比癌旁组织高6倍(P=0.002),而ACE2在HCC和癌旁组织之间没有统计学差异。在35%(7/20)的CHB患者中检测到肝细胞ACE2表达,并且主要分布在炎症区域。然而,有或没有炎症的区域之间的TMPRSS2表达没有差异。IFN-α2b轻微诱导ACE2表达(2.4倍,P=0.033)在HepG2细胞中,但在Huh-7,QSG-7701和L-02细胞中没有。IFN-α2b不影响这些细胞系中的TMPRSS2表达。此外,HBV复制并未改变HepAD38细胞中ACE2的表达。
尽管HBV复制并不直接影响ACE2和TMPRSS2的表达,但在某些患者中,肝内炎症和癌变可能会增加其表达,which,反过来,可能促进SARS-CoV-2在肝细胞中的感染。
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