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2015 ; 12
(3
): 3453-3461
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Inhibition of liver fibrosis using vitamin A-coupled liposomes to deliver matrix
metalloproteinase-2 siRNA in vitro
#MMPMID26017616
Li Y
; Liu F
; Ding F
; Chen P
; Tang M
Mol Med Rep
2015[Sep]; 12
(3
): 3453-3461
PMID26017616
show ga
Hepatic fibrosis is a common form of wound healing in response to chronic liver
injuries and can lead to more serious complications, including mortality. It is
well?established that hepatic stellate cells (HSCs) are central mediators of
hepatic fibrosis, and matrix metalloproteinase?2 (MMP?2) is important in the
formation of liver fibrosis. In addition, HSCs are the primary cells secreting
MMP?2 and extracellular matrix, therefore, there has been increasing interest in
developing agents with high selectivity towards HSCs. However, no clinical drugs
based on MMP?2, directed against HSCs, have been used to prevent fibrosis.
Following consideration of the abundant vitamin A (VitA) receptors expressed on
the cellular membrane of HSCs, the present study constructed VitA?coupled
liposomes (VitA?lips) using dicyclohexylcarbodiimide?1, 3?diaminopentane
condensation, rotatory film processing and ultrasonic oscillation. The results
revealed that the liposomes exhibited low cytotoxicity and a suitable binding
ability to MMP?2 small interference (si)RNA. Furthermore, the liposomes
effectively delivered MMP?2 siRNA to the HSC?T6 cells. When HSCs were treated
with the liposomes carrying MMP?2 siRNA (VitA?lip?MMP?2 siRNA), the mRNA
expression and activity of MMP?2, and the protein expression levels of ??smooth
muscle actin and type I collagen were significantly reduced. These results
suggested that inhibition of the expression of MMP?2 in HSC?T6 cells may
contribute to preventing hepatic fibrosis, and provided experimental support to
the development of specific drugs against MMP?2 to prevent fibrogenesis in
chronic liver disease.