کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1930497 | 1050516 | 2011 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Tissue factor dependent liver injury causes release of retinoid receptors (RXR-α and RAR-α) as lipid droplets Tissue factor dependent liver injury causes release of retinoid receptors (RXR-α and RAR-α) as lipid droplets](/preview/png/1930497.png)
Hepatic stellate cells (HSC) store retinoids and upon activation differentiate into myofibroblast-like cells, a process whereby they lose their retinoid-containing lipid droplets. We reported earlier, activation of tissue factor (TF) in our MCT/LPS hepatotoxicity model. We now report the involvement of TF in the release of retinoid receptors RAR-α and RXR-α as accumulated lipid droplet during monocrotaline/lipopolysaccharide (MCT/LPS)-liver injury. Constitutive expression of RAR-α was observed in HSCs and endothelial cells of bile duct and portal vein, while expression of RXR-α was observed in certain pericentral hepatocytes and HSCs. Administration of sub-toxic doses of MCT or LPS strongly increased TF and RXR-α but not RAR-α expressions in HSCs and hepatocytes. However MCT/LPS co-treatment showed insoluble droplets containing RAR-α and RXR-α in the vicinity of the necrotic areas. Blocking TF with TF antisense oligonucleotides (TF-AS ODN) led to normal hepatocyte expression of RXR-α and upregulated the expression of RAR-α in HSCs. This study shows clear evidence of in vivo release of RAR-α and RXR-α as insoluble lipid droplets in liver injury. It is possible that these insoluble droplets of RAR-α and RXR-α could be used as markers for liver injury in general and activation of HSCs in particular. RXR-α appears to be a more sensitive than RAR-α as it was affected by even the subtoxic doses of MCT or LPS. The fact that TF-AS treatment not only down-regulated TF but also obliterated the release of RAR-α and RXR-α as insoluble lipid droplets in hepatocytes points towards TF being an important regulatory molecule for RAR-α and RXR-α.
► Retinoid receptors RAR-α and RXR-α are released as lipid droplets in liver injury induced by monocrotaline (MCT)/lipopolysaccharide (LPS).
► RAR-α and RXR-α could be used as markers for liver injury in general and activation of HSCs in particular.
► RXR-α appears to be a more sensitive than RAR-α as it was affected by even the subtoxic doses of MCT or LPS.
► Tissue factor (TF) is an important regulatory molecule for RAR-α and RXR-α.
Journal: Biochemical and Biophysical Research Communications - Volume 410, Issue 1, 24 June 2011, Pages 146–151