Matches in SemOpenAlex for { <https://semopenalex.org/work/W3016360730> ?p ?o ?g. }
Showing items 1 to 87 of
87
with 100 items per page.
- W3016360730 endingPage "1" @default.
- W3016360730 startingPage "1" @default.
- W3016360730 abstract "Introduction Acetaminophen (APAP) induced acute liver failure (ALF) is recognized as the most common cause of ALF in Western societies, occurring in approximately 40% of all cases. The disease is characterized by coagulopathy, hepatic encephalopathy, multi-organ failure, and death. Micro-RNAs are small, non-coding RNAs capable of altering gene expression at the post-transcriptional level. MicroRNA-21 is dynamically expressed in the liver and several target genes of microRNA-21 are highly expressed in the pericentral hepatocytes. We hypothesize that microRNA-21 genetic ablation attenuates hepatotoxicity following acetaminophen intoxication. Methods Eight-week old microRNA-21 knockout (miR21KO) or wild-type (WT) C57BL/6N male mice were injected with acetaminophen (APAP, 300 mg/kg BW) or saline. Animals were sacrificed 6 or 24 hours post-injection, and serum and livers were harvested. Results WT animals showed significantly higher hepatic injury markers serum ALT (20,077±2,084 U/L vs 13,364±1,667 U/L, p<0.05, n=11) and AST (29,125±3,485 U/L vs 20,282±2,445 U/L, p<0.05, n=11) than their miR21KO counterparts after 6 hours of APAP treatment, while no significant difference was observed in animals treated for 24 hours. miR21KO mice presented attenuated liver necrosis compared with WT animals (59.8±5.8 vs 42.5±7.9 %, p<0.05, n=10) 24 hours post-APAP treatment. Moreover, miR21KO mice had decreased hepatic DNA fragmentation analyzed by TUNEL assay than WT animals (58.26±4.5 vs 42.60±4.9 %, p<0.05, n=8) after 24 hours of APAP treatment. MicroRNA-21 ablation did not modify hepatic GSSH/GSH or APAP-Cysteine adducts at either 6 or 24 hours post treatment. MicroRNA-21 ablation upregulated mRNA expression of autophagy (Beclin-1, Map1LC3a, Pdcd4, p62) and decreased inflammation (PAI-1) markers compared with WT mice 24 post APAP treatment. MicroRNA-21 ablation exacerbated hepatic autophagy marker LC3A/B-II protein expression at both 6 (2.8 vs 1.5-fold) and 24 (2.2 vs 1.2-fold 1.2) hours post APAP, correlating with increased Map1lc3a/b mRNA levels. Conclusion Our results suggest that miRNA-21 mediates APAP-induced hepatotoxicity. MicroRNA-21 inhibition could be a novel therapeutic approach to abolish or mitigate APAP-induced hepatotoxicity. The beneficial effect of microRNA-21 is due to an upregulation of hepatic autophagy. Specifically, microRNA-21 inhibition could be particularly useful when APAP intoxication is detected at its late stages and the only available therapy, NAC, is minimally effective. Support or Funding Information Supported by NIH grants R21 DK-113500 and P20 GM-121334." @default.
- W3016360730 created "2020-04-24" @default.
- W3016360730 creator A5001142311 @default.
- W3016360730 creator A5002898172 @default.
- W3016360730 creator A5011991388 @default.
- W3016360730 creator A5018878293 @default.
- W3016360730 creator A5042873739 @default.
- W3016360730 creator A5077581148 @default.
- W3016360730 creator A5082512025 @default.
- W3016360730 creator A5086563558 @default.
- W3016360730 date "2020-04-01" @default.
- W3016360730 modified "2023-10-05" @default.
- W3016360730 title "MicroRNA‐21 Ablation Attenuates Acetaminophen‐Induced Hepatoxtoxicity in Male Mice" @default.
- W3016360730 doi "https://doi.org/10.1096/fasebj.2020.34.s1.03494" @default.
- W3016360730 hasPublicationYear "2020" @default.
- W3016360730 type Work @default.
- W3016360730 sameAs 3016360730 @default.
- W3016360730 citedByCount "0" @default.
- W3016360730 crossrefType "journal-article" @default.
- W3016360730 hasAuthorship W3016360730A5001142311 @default.
- W3016360730 hasAuthorship W3016360730A5002898172 @default.
- W3016360730 hasAuthorship W3016360730A5011991388 @default.
- W3016360730 hasAuthorship W3016360730A5018878293 @default.
- W3016360730 hasAuthorship W3016360730A5042873739 @default.
- W3016360730 hasAuthorship W3016360730A5077581148 @default.
- W3016360730 hasAuthorship W3016360730A5082512025 @default.
- W3016360730 hasAuthorship W3016360730A5086563558 @default.
- W3016360730 hasBestOaLocation W30163607301 @default.
- W3016360730 hasConcept C104317684 @default.
- W3016360730 hasConcept C126322002 @default.
- W3016360730 hasConcept C134018914 @default.
- W3016360730 hasConcept C145059251 @default.
- W3016360730 hasConcept C16685009 @default.
- W3016360730 hasConcept C190283241 @default.
- W3016360730 hasConcept C196795494 @default.
- W3016360730 hasConcept C204232928 @default.
- W3016360730 hasConcept C2776637226 @default.
- W3016360730 hasConcept C2777075537 @default.
- W3016360730 hasConcept C2777214474 @default.
- W3016360730 hasConcept C2777397205 @default.
- W3016360730 hasConcept C2778722691 @default.
- W3016360730 hasConcept C31573885 @default.
- W3016360730 hasConcept C43759708 @default.
- W3016360730 hasConcept C55493867 @default.
- W3016360730 hasConcept C71924100 @default.
- W3016360730 hasConcept C86803240 @default.
- W3016360730 hasConcept C98274493 @default.
- W3016360730 hasConceptScore W3016360730C104317684 @default.
- W3016360730 hasConceptScore W3016360730C126322002 @default.
- W3016360730 hasConceptScore W3016360730C134018914 @default.
- W3016360730 hasConceptScore W3016360730C145059251 @default.
- W3016360730 hasConceptScore W3016360730C16685009 @default.
- W3016360730 hasConceptScore W3016360730C190283241 @default.
- W3016360730 hasConceptScore W3016360730C196795494 @default.
- W3016360730 hasConceptScore W3016360730C204232928 @default.
- W3016360730 hasConceptScore W3016360730C2776637226 @default.
- W3016360730 hasConceptScore W3016360730C2777075537 @default.
- W3016360730 hasConceptScore W3016360730C2777214474 @default.
- W3016360730 hasConceptScore W3016360730C2777397205 @default.
- W3016360730 hasConceptScore W3016360730C2778722691 @default.
- W3016360730 hasConceptScore W3016360730C31573885 @default.
- W3016360730 hasConceptScore W3016360730C43759708 @default.
- W3016360730 hasConceptScore W3016360730C55493867 @default.
- W3016360730 hasConceptScore W3016360730C71924100 @default.
- W3016360730 hasConceptScore W3016360730C86803240 @default.
- W3016360730 hasConceptScore W3016360730C98274493 @default.
- W3016360730 hasIssue "S1" @default.
- W3016360730 hasLocation W30163607301 @default.
- W3016360730 hasOpenAccess W3016360730 @default.
- W3016360730 hasPrimaryLocation W30163607301 @default.
- W3016360730 hasRelatedWork W2030482078 @default.
- W3016360730 hasRelatedWork W2053020665 @default.
- W3016360730 hasRelatedWork W2065628698 @default.
- W3016360730 hasRelatedWork W2091960754 @default.
- W3016360730 hasRelatedWork W2110136270 @default.
- W3016360730 hasRelatedWork W2145234092 @default.
- W3016360730 hasRelatedWork W2332279323 @default.
- W3016360730 hasRelatedWork W2361249409 @default.
- W3016360730 hasRelatedWork W3028704232 @default.
- W3016360730 hasRelatedWork W4245814771 @default.
- W3016360730 hasVolume "34" @default.
- W3016360730 isParatext "false" @default.
- W3016360730 isRetracted "false" @default.
- W3016360730 magId "3016360730" @default.
- W3016360730 workType "article" @default.