Hepatic retinoid stores are required for normal liver regeneration[S]
| Autor: | Shmarakov Io, William S. Blaner, Hongfeng Jiang, Ira J. Goldberg, Kryscilla Jian Zhang Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class retinyl ester lipid droplet Tretinoin QD415-436 Biology Real-Time Polymerase Chain Reaction Biochemistry vitamin A Mice Retinoids Endocrinology Tandem Mass Spectrometry Internal medicine Lipid droplet medicine Animals Retinoid Research Articles Triglycerides Mice Knockout Cell growth Regeneration (biology) Cell Biology Cell cycle Immunohistochemistry Liver regeneration Liver Regeneration cell proliferation nuclear hormone receptor Liver Acyltransferase cell cycle medicine.drug Endocannabinoids |
| Zdroj: | Journal of Lipid Research, Vol 54, Iss 4, Pp 893-908 (2013) |
| Popis: | Preliminary studies of liver regeneration induced by partial hepatectomy (PHE) identified a substantial depletion of hepatic retinoid stores, by greater than 70%, in regenerating livers of wild-type C57Bl/6J mice. To understand this, we compared responses of wild-type and lecithin:retinol acyltransferase (Lrat)-deficient mice, which totally lack hepatic retinoid stores, to PHE. The Lrat-deficient livers showed delayed regeneration in the first 24 h after PHE. At 12 h after PHE, we observed significantly less mRNA expression for growth factors and cytokines implicated in regulating the priming phase of liver regeneration, specifically for Hgf and Tgfα, but not Tgfβ. Compared with wild-type mice, the changes in mRNA levels for p21 and cyclins E1, B1, and A2 mRNAs and for hepatocellular BrdU incorporation and mitoses were delayed (i.e., shifted to later times) in regenerating Lrat(-/-) livers. Concentrations of all-trans-retinoic acid were significantly lower in the livers of Lrat(-/-) mice following PHE, and this was accompanied by diminished expression of known retinoid-responsive genes. At later times after PHE, the rate of liver weight restoration for Lrat(-/-) mice was parallel to that of wild-type mice, although additional biochemical differences were observed. Thus, hepatic retinoid stores are required for maintaining expression of signaling molecules that regulate cell proliferation and differentiation immediately after hepatic injury, accounting for the delayed restoration of liver mass in Lrat(-/-) mice. |
| Databáze: | OpenAIRE |
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