Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an ele...Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl_(4))-treated mice and patients with cirrhosis.Deletion of Pafah1b3 significantly attenuated CCl_(4)-induced fibrosis,hepatic stellate cell(HSC)activation,and activation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-βreceptor 1(TβR1),which subsequently decreases TbR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl_(4)-induced fibrosis in mice.Furthermore,Pafah1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafah1b3 in modulating TGF-βsignaling and driving HSC activation.展开更多
Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types...Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types of human malignancies.However,the precise role and mechanisms of PAFAH1B3 in LUAD are still unknown.Therefore,we will initially explore the effect of PAFAH1B3 on LUAD in this study.Methods In this study,we first performed a pan-cancer analysis of PAFAH1B3 expression and prognosis using The Cancer Genome Atlas(TCGA),genotype-tissue expression(GTEx)data,and GEPIA database.Next,the relationship between PAFAH1B3 expression and LUAD immune infiltration and pyroptosis-related genes was explored by GEPIA database and TIMER database.The effect of PAFAH1B3 on LUAD was further explored by CCK-8,wound healing,and Transwell assays.Finally,non-coding RNA(ncRNA)that may be involved in the regulation of PAFAH1B3 was explored using Starbase database analysis.Results The results found that PAFAH1B3 may be an oncogene in LUAD and has a significant adverse relationship with tumor immune cell infiltration,immune cell biomarkers and pyroptosis-related gene expression.Meanwhile,cell experiments also found that PAFAH1B3 knockout significantly reduced the proliferation,migration and invasion of A549 cells.Conclusions PAFAH1B3 high expression in LUAD patients is associated with poor prognosis,tumor immune infiltration,and cell pyroptosis gene expression.展开更多
本试验旨在测定和比较5个绿壳蛋鸡群体中EAV-HP在溶质载体有机阴离子转运蛋白家族成员1B3（solute carrier organic anion transporter family member 1B3,SLCO1B3）基因的5′-非编码区插入整合的频率和类型。所选5个绿壳蛋鸡群体包括3...本试验旨在测定和比较5个绿壳蛋鸡群体中EAV-HP在溶质载体有机阴离子转运蛋白家族成员1B3（solute carrier organic anion transporter family member 1B3,SLCO1B3）基因的5′-非编码区插入整合的频率和类型。所选5个绿壳蛋鸡群体包括3个北京地区的商业群体（北京-LK、北京-LF和北京-YM）、贵州长顺绿壳蛋鸡群体和四川省地方品种旧院黑鸡;采用双重PCR对EAV-HP的插入整合进行检测,并利用DNA测序的方法判断EAV-HP的主要突变位点。结果表明,5个绿壳蛋鸡群体均拥有一定数量的EAV-HP插入整合的个体,表现为杂合（LC/N）和纯合（LC/LC）基因型,均可产绿壳蛋,其中旧院黑鸡的绿壳蛋频率最低,仅为28.90%,其次是北京-LF群体,为46.94%,其他3个群体的绿壳蛋频率为83.33%~84.62%;经卡方检验,北京-LF和旧院黑鸡群体符合Hardy-Weinberg平衡（P〉0.05）,而其他3个群体则极显著偏离Hardy-Weinberg平衡状态（P〈0.01）。DNA测序结果显示这5个绿壳蛋鸡群体中EAV-HP插入整合的序列与之前报道的东乡绿壳蛋鸡的KC632577.1完全一致。地方品种旧院黑鸡的绿壳蛋频率较低,建议利用双重PCR检测的分子标记辅助选择方法加以提高。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81873576)Wenzhou Municipal Science and Technology Bureau,China(Grant No.:Y20220023).
文摘Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl_(4))-treated mice and patients with cirrhosis.Deletion of Pafah1b3 significantly attenuated CCl_(4)-induced fibrosis,hepatic stellate cell(HSC)activation,and activation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-βreceptor 1(TβR1),which subsequently decreases TbR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl_(4)-induced fibrosis in mice.Furthermore,Pafah1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafah1b3 in modulating TGF-βsignaling and driving HSC activation.
基金supported by the National Postdoctoral Innovation Talents Support Program of China,and National Natural Science Foundation of China(No.82303564).
文摘Background Lung adenocarcinoma(LUAD)is a common cancer with a poor prognosis.Platelet-activating factor acetylhydrolase,isoform Ib,gamma subunit 29 kDa(PAFAH1B3)plays an important role in the development of many types of human malignancies.However,the precise role and mechanisms of PAFAH1B3 in LUAD are still unknown.Therefore,we will initially explore the effect of PAFAH1B3 on LUAD in this study.Methods In this study,we first performed a pan-cancer analysis of PAFAH1B3 expression and prognosis using The Cancer Genome Atlas(TCGA),genotype-tissue expression(GTEx)data,and GEPIA database.Next,the relationship between PAFAH1B3 expression and LUAD immune infiltration and pyroptosis-related genes was explored by GEPIA database and TIMER database.The effect of PAFAH1B3 on LUAD was further explored by CCK-8,wound healing,and Transwell assays.Finally,non-coding RNA(ncRNA)that may be involved in the regulation of PAFAH1B3 was explored using Starbase database analysis.Results The results found that PAFAH1B3 may be an oncogene in LUAD and has a significant adverse relationship with tumor immune cell infiltration,immune cell biomarkers and pyroptosis-related gene expression.Meanwhile,cell experiments also found that PAFAH1B3 knockout significantly reduced the proliferation,migration and invasion of A549 cells.Conclusions PAFAH1B3 high expression in LUAD patients is associated with poor prognosis,tumor immune infiltration,and cell pyroptosis gene expression.
文摘本试验旨在测定和比较5个绿壳蛋鸡群体中EAV-HP在溶质载体有机阴离子转运蛋白家族成员1B3（solute carrier organic anion transporter family member 1B3,SLCO1B3）基因的5′-非编码区插入整合的频率和类型。所选5个绿壳蛋鸡群体包括3个北京地区的商业群体（北京-LK、北京-LF和北京-YM）、贵州长顺绿壳蛋鸡群体和四川省地方品种旧院黑鸡;采用双重PCR对EAV-HP的插入整合进行检测,并利用DNA测序的方法判断EAV-HP的主要突变位点。结果表明,5个绿壳蛋鸡群体均拥有一定数量的EAV-HP插入整合的个体,表现为杂合（LC/N）和纯合（LC/LC）基因型,均可产绿壳蛋,其中旧院黑鸡的绿壳蛋频率最低,仅为28.90%,其次是北京-LF群体,为46.94%,其他3个群体的绿壳蛋频率为83.33%~84.62%;经卡方检验,北京-LF和旧院黑鸡群体符合Hardy-Weinberg平衡（P〉0.05）,而其他3个群体则极显著偏离Hardy-Weinberg平衡状态（P〈0.01）。DNA测序结果显示这5个绿壳蛋鸡群体中EAV-HP插入整合的序列与之前报道的东乡绿壳蛋鸡的KC632577.1完全一致。地方品种旧院黑鸡的绿壳蛋频率较低,建议利用双重PCR检测的分子标记辅助选择方法加以提高。
