Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

Targeting uridine diphosphate glucuronosyltransferase 1A1 in liver disease:Current research and future directions

The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.

Genetic analysison the association between polymorphisms of UGT1A1and GST and neonatal hyperbilirubinemia

Objective:To investigate whether polymorphisms of uridine diphosphoglucuronate-glucuronosyltransferase 1A1(UGT1A1)c.211G>A and glutathione S transferases(GST)gene(GSTT1and GSTM1)are associated with neonatal hyperbilirubinemia.Methods:A case-control study was performed.A multiplex polymerase chain reaction(PCR)was used to detect the GSTT1and GSTM1polymorphisms.Single nucleotide polymorphism of UGT1A1c.211G>A was identified by PCR combined with DNA sequencing.The effects and co-expression of UGT1A1c.211G>A,GSTT1and GSTM1gene polymorphisms on the development of neonatal hyperbilirubinemia were estimated.Results:A allele frequency of c.211G>A polymorphism of UGT1A1gene was 0.186in case group and 0.086in control group,respectively.A allele frequency of the polymorphism of UGT1A1gene in the case group was higher than that of the control group(χ2=5.968,P=0.022).The frequencies of GSTT1and GSTM1in the case group were similar to that of the control groups.Logistic regression analysis showed that UGT1A1c.211G>A variant and UGT1A1+GSTM1 mutation affected neonatal hyperbilirubinemia.Conclusion:UGT1A1c.211G>A gene polymorphism may be one risk factor involved in the development of neonatal hyperbilirubinemia,and GST gene polymorphism may not be associated with the development of neonatal hyperbilirubinemia in our study.The co-expression of UGT1A1c.211G>A and GSTM1polymorphisms may reduce the risk for neonatal hyperbilirubinemia development.