Article(id=1259888469678145884, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1259888457367806489, articleNumber=null, orderNo=null, doi=10.13343/j.cnki.wsxb.20250817, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1761840000000, receivedDateStr=2025-10-31, revisedDate=null, revisedDateStr=null, acceptedDate=1764259200000, acceptedDateStr=2025-11-28, onlineDate=1778310418767, onlineDateStr=2026-05-09, pubDate=1777824000000, pubDateStr=2026-05-04, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1778310418767, onlineIssueDateStr=2026-05-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1778310418767, creator=13701087609, updateTime=1778310418767, updator=13701087609, issue=Issue{id=1259888457367806489, tenantId=1146029695717560320, journalId=1192105938417971205, year='2026', volume='66', issue='5', pageStart='2031', pageEnd='2556', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=0, articleOrder=1, issueType=-1, specialIssue=null, createTime=1778310415832, creator=13701087609, updateTime=1778320153326, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1259929299465921482, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1259888457367806489, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1259929299465921483, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1259888457367806489, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2404, endPage=2415, ext={EN=ArticleExt(id=1259888471347478902, articleId=1259888469678145884, tenantId=1146029695717560320, journalId=1192105938417971205, language=EN, title=Changes in Agap2 expression in hepatic fibrosis induced by hepatitis E virus infection, columnId=1192149543992045670, journalTitle=Acta Microbiologica Sinica, columnName=Research Article, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate changes in ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 (Agap2) expression during hepatic fibrosis progression following hepatitis E virus (HEV) infection and preliminarily explore the association between chronic HEV infection and Agap2 expression. Methods A BALB/c mouse model of HEV infection was established through inoculation in tail vein and subjected to RNA sequencing. HEV infection and Agap2 expression in the liver tissue were detected via immunohistochemistry, immunofluorescence assay, and real-time qPCR. Results Agap2 expression was upregulated following HEV infection (24 hpi group: P=0.000 3, 48 hip group: P=0.001 9). Chronic HEV infection induced hepatic fibrosis in mice, and Agap2 expression in the mouse liver was positively correlated with HEV load (r=0.797 4, P<0.000 1). Similarly, in vitro experiments demonstrated that Agap2 expression was upregulated in HEV-infected Huh 7.5.1 cells (r=0.968 3, P=0.002 4) and LX-2 cells (r=0.683 5, P=0.006 5), showing a positive correlation with HEV load. Conclusion The results demonstrate that Agap2 expression is positively correlated with HEV load during hepatic fibrosis progression after chronic HEV infection. Agap2 may serve as a potential molecular target for the treatment of HEV-associated hepatic fibrosis.

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目的 探究戊型肝炎病毒(hepatitis E virus, HEV)感染后肝脏纤维化进程中具有GTP结合蛋白样结构域、锚蛋白重复序列和PH结构域2的Arf GAP (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2, Agap2)的表达变化，并初步探究HEV慢性化感染与Agap2表达之间的关联。 方法 通过尾静脉接种HEV构建HEV感染的BALB/c小鼠模型，并进行全转录组测序。利用免疫组化、免疫荧光和实时荧光定量PCR方法检测感染HEV的BALB/c小鼠肝脏中HEV感染情况及Agap2表达情况。 结果 研究发现HEV感染后Agap2表达显著上升(24 hpi感染组P=0.000 3，48 hpi感染组P=0.001 9)。HEV慢性化感染会导致小鼠肝纤维化发生，且经检测发现小鼠肝脏中Agap2的表达与HEV病毒载量呈正相关(r=0.797 4，P<0.000 1)。通过体外实验同样发现，Agap2在HEV感染的Huh 7.5.1 (r=0.968 3，P=0.002 4)和LX-2 (r=0.683 5，P=0.006 5)细胞系中表达呈上调趋势，与HEV病毒载量呈正相关。 结论 本研究表明，在HEV慢性化感染后肝脏纤维化进程中Agap2的表达与HEV病毒载量呈正相关，Agap2可能是治疗HEV感染中肝纤维化的潜在新分子靶标。

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Phytomedicine, 2022, 105: 154349., articleTitle=Demethylzeylasteral attenuates hepatic stellate cell activation and liver fibrosis by inhibiting AGAP2 mediated signaling, refAbstract=null)], funds=[Fund(id=1259928452250124509, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, awardId=202401AS070057, language=EN, fundingSource=The Yunnan Provincial Natural Science Foundation(202401AS070057), fundOrder=null, country=null), Fund(id=1259928453541970150, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, awardId=202401AS070057, language=CN, fundingSource=云南省自然科学基金(202401AS070057), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1259928399930377041, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, xref=1., ext=[AuthorCompanyExt(id=1259928400257532754, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, companyId=1259928399930377041, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^1.Medical School, Kunming University of Science and Technology, Kunming, Yunnan, China), AuthorCompanyExt(id=1259928400261727059, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, companyId=1259928399930377041, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^1.昆明理工大学 医学院，云南 昆明)]), AuthorCompany(id=1259928401561961316, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, xref=2., ext=[AuthorCompanyExt(id=1259928401616487269, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, companyId=1259928401561961316, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^2.Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, Yunnan, China), AuthorCompanyExt(id=1259928402002363238, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, companyId=1259928401561961316, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^2.云南省临床病毒学重点实验室，云南 昆明)])], figs=[ArticleFig(id=1259928434269143150, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=EN, label=Figure 1, caption=Successful replication of HEV in BALB/c mice. A: Immunohistochemical detection of HEV ORF3 protein in mouse liver (black arrow); B: Quantification of HEV ORF3-positive cells in immunohistochemistry; C: Immunofluorescence detection of HEV ORF3 protein in mouse liver, with nuclei (blue) stained by DAPI; D: Quantification of HEV ORF3 fluorescence signal intensity; E: Viral load in stool of HEV-infected mice; F: Viral load in liver tissues of HEV-infected mice. **: P<0.01; ***: P<0.001., figureFileSmall=raMrZss6u/E1rLqMYi/fGA==, figureFileBig=KKJrKV9qEveJ3sLkMaipTg==, tableContent=null), ArticleFig(id=1259928435456131192, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=CN, label=图1, caption=HEV在BALB/c小鼠中成功复制, figureFileSmall=raMrZss6u/E1rLqMYi/fGA==, figureFileBig=KKJrKV9qEveJ3sLkMaipTg==, tableContent=null), ArticleFig(id=1259928438517973130, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=EN, label=Figure 2, caption=Gene sequencing screening for differential gene Agap2. A: Gene functional enrichment analysis comparing the 24 hpi infected group with the control group; B: Gene functional enrichment analysis comparing the 48 hpi infected group with the control group; C and D: Volcano plot and Venn diagram highlighting Agap2 as a differentially expressed gene at both infection time points; E: Relative mRNA expression levels of Agap2 at different time points (**: P<0.01; ***: P<0.001); F: Analysis of the ENCORI database indicating upregulated Agap2 expression in patients with liver hepatocellular carcinoma (LIHC)., figureFileSmall=mE+CV5fD+91myftzKxwUxQ==, figureFileBig=xOskQbJ5L8Ux9PDUDlux6Q==, tableContent=null), ArticleFig(id=1259928440220860569, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=CN, label=图2, caption=差异基因Agap2的筛选, figureFileSmall=mE+CV5fD+91myftzKxwUxQ==, figureFileBig=xOskQbJ5L8Ux9PDUDlux6Q==, tableContent=null), ArticleFig(id=1259928441034555557, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=EN, label=Figure 3, caption=Chronic HEV infection mode. A: BALB/c mouse model of chronic HEV infection was successfully established; B: Correlation analysis between hepatic HEV RNA levels and relative Agap2 mRNA expression at different time points; C and D: In vitro validation of the correlation between viral load and Agap2 expression in cell experiments (Huh 7.5.1 and LX-2 cell lines)., figureFileSmall=hdCWS2WEov4J3G/0p8qKtw==, figureFileBig=Kvt8v+puvWOZWZDO9G+Qng==, tableContent=null), ArticleFig(id=1259928443878293677, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=CN, label=图3, caption=HEV慢性感染小鼠模型, figureFileSmall=hdCWS2WEov4J3G/0p8qKtw==, figureFileBig=Kvt8v+puvWOZWZDO9G+Qng==, tableContent=null), ArticleFig(id=1259928445098836154, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=EN, label=Figure 4, caption=Liver fibrosis in mice with chronic HEV infection. Immunohistochemistry, Masson’s trichrome staining, and immunofluorescence were used to detect α-SMA in the livers of BALB/c mice from the control group and the HEV chronically infected group (A), perform liver histopathological analysis (C), and conduct apoptosis detection (E); B: Percentage of α-SMA-positive cells; D: Masson’s trichrome staining score; F: Percentage of apoptosis-positive signals, with nuclei (blue) labeled by DAPI staining; G: Radar chart comparing overall features between control and infected groups (85-240 dpi). ***: P<0.001; *: P<0.05; ns: No significant difference., figureFileSmall=luCtpneFds1FtsHZtRSPSQ==, figureFileBig=tYexM4bRQhBKS0Wgow//rw==, tableContent=null), ArticleFig(id=1259928447628001480, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1259888469678145884, language=CN, label=图4, caption=HEV慢性感染小鼠肝纤维化, figureFileSmall=luCtpneFds1FtsHZtRSPSQ==, figureFileBig=tYexM4bRQhBKS0Wgow//rw==, tableContent=null)], attaches=null, 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