目的探索细胞外基质在疝组织改变或由于成纤维细胞转?缺陷导致切口疝发生过程中培养的成纤维细胞中I型胶原mRNA和III型胶原mRNA表达。方法成纤维细胞来自切口疝病人和复发性切口疝病人,对照组来自正常健康组织而没有经过手术皮肤病人和...目的探索细胞外基质在疝组织改变或由于成纤维细胞转?缺陷导致切口疝发生过程中培养的成纤维细胞中I型胶原mRNA和III型胶原mRNA表达。方法成纤维细胞来自切口疝病人和复发性切口疝病人,对照组来自正常健康组织而没有经过手术皮肤病人和虽有切口癍痕但无临床表现切口疝病人。用RT-PCR和North-ern B lotting确定I型胶原mRNA对III型胶原mRNA比率。结果RT-PCR结果表明了I型胶原mRNA在切口疝病人(0.90±0.04)和复发性切口疝病人(1.19±0.04)组中,标相应地在癍痕组织(0.54±0.02)和健康组织(0.43±0.01)。然而III型胶原mRNA在切口疝病人显著增加至4.13±0.04和复发性切口疝病人增加至6.02±0.03,而在癍痕组织2.29±0.04,在健康组织中为1.72±0.03。疝病人的成纤维细胞I型胶原mRNA对III型胶原mRNA比率显著减少(P<0.01)。结论在培养的皮肤成纤维细胞中I型胶原mRNA对III型胶原mRNA的比率减少,表明在切口疝病人存在胶原蛋白代谢紊乱。因此一个损伤的伤口愈合过程可能解释临床缝合修补疝组织不尽满意结果的原因。展开更多
Acetaminophen(APAP)overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States.We investigated the role of p62/SQSTM1(referred to as p62)in APAP-induced liver injury(AIL...Acetaminophen(APAP)overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States.We investigated the role of p62/SQSTM1(referred to as p62)in APAP-induced liver injury(AILI)in mice.We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment,which was inversely correlated with the hepatic levels of APAPadducts.APAP also activated mTOR at 24 h,which is associated with increased cell proliferation.In contrast,p62 knockout(KO)mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment.Surprisingly,p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h.We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor(VWF)and platelet aggregation,which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment.Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.展开更多
文摘目的探索细胞外基质在疝组织改变或由于成纤维细胞转?缺陷导致切口疝发生过程中培养的成纤维细胞中I型胶原mRNA和III型胶原mRNA表达。方法成纤维细胞来自切口疝病人和复发性切口疝病人,对照组来自正常健康组织而没有经过手术皮肤病人和虽有切口癍痕但无临床表现切口疝病人。用RT-PCR和North-ern B lotting确定I型胶原mRNA对III型胶原mRNA比率。结果RT-PCR结果表明了I型胶原mRNA在切口疝病人(0.90±0.04)和复发性切口疝病人(1.19±0.04)组中,标相应地在癍痕组织(0.54±0.02)和健康组织(0.43±0.01)。然而III型胶原mRNA在切口疝病人显著增加至4.13±0.04和复发性切口疝病人增加至6.02±0.03,而在癍痕组织2.29±0.04,在健康组织中为1.72±0.03。疝病人的成纤维细胞I型胶原mRNA对III型胶原mRNA比率显著减少(P<0.01)。结论在培养的皮肤成纤维细胞中I型胶原mRNA对III型胶原mRNA的比率减少,表明在切口疝病人存在胶原蛋白代谢紊乱。因此一个损伤的伤口愈合过程可能解释临床缝合修补疝组织不尽满意结果的原因。
基金supported by fundings U01 AA024733,R37 AA020518,R21 AA027250,R01 DK102142,and R01 AG072895(USA)。
文摘Acetaminophen(APAP)overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States.We investigated the role of p62/SQSTM1(referred to as p62)in APAP-induced liver injury(AILI)in mice.We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment,which was inversely correlated with the hepatic levels of APAPadducts.APAP also activated mTOR at 24 h,which is associated with increased cell proliferation.In contrast,p62 knockout(KO)mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment.Surprisingly,p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h.We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor(VWF)and platelet aggregation,which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment.Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.
