Plumbagin Alleviates Capillarization of Hepatic Sinusoids In Vitro by Downregulating ET-1, VEGF, LN, and Type IV Collagen.

Abstract

Critical roles for liver sinusoidal endothelial cells (LSECs) in liver fibrosis have been demonstrated, while little is known regarding the underlying molecular mechanisms of drugs delivered to the LSECs. Our previous study revealed that plumbagin plays an antifibrotic role in liver fibrosis. In this study, we investigated whether plumbagin alleviates capillarization of hepatic sinusoids by downregulating endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), laminin (LN), and type IV collagen on leptin-stimulated LSECs. We found that normal LSECs had mostly open fenestrae and no organized basement membrane. Leptin-stimulated LSECs showed the formation of a continuous basement membrane with few open fenestrae, which were the features of capillarization. Expression of ET-1, VEGF, LN, and type IV collagen was enhanced in leptin-stimulated LSECs. Plumbagin was used to treat leptin-stimulated LSECs. The sizes and numbers of open fenestrae were markedly decreased, and no basement membrane production was found after plumbagin administration. Plumbagin decreased the levels of ET-1, VEGF, LN, and type IV collagen in leptin-stimulated LSECs. Plumbagin promoted downregulation of ET-1, VEGF, LN, and type IV collagen mRNA. Altogether, our data reveal that plumbagin reverses capillarization of hepatic sinusoids by downregulation of ET-1, VEGF, LN, and type IV collagen.

• Authors: Guiyu Li, Yue Peng, Tiejian Zhao, Jiyong Lin, Xuelin Duan, Yanfei Wei, Jing Ma
• Journal: BioMed research international (Biomed Res Int) Vol. 2017 Pg. 5603216 ( 2017) ISSN: 2314-6141 [Electronic] United States
• PMID: 28770223 (Publication Type: Journal Article)

Chemical References

• Collagen Type IV
• Endothelin-1
• Laminin
• Naphthoquinones
• Vascular Endothelial Growth Factor A
• plumbagin

Topics

• Animals
• Basement Membrane (drug effects, metabolism)
• Capillaries (drug effects, metabolism)
• Collagen Type IV (metabolism)
• Down-Regulation (drug effects)
• Endothelial Cells (metabolism)
• Endothelin-1 (metabolism)
• Hepatic Veins (drug effects, metabolism)
• Hepatocytes (drug effects, metabolism)
• Laminin (metabolism)
• Liver (drug effects, metabolism)
• Liver Cirrhosis
• Male
• Naphthoquinones (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vascular Endothelial Growth Factor A (metabolism)