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Inhibition of liver fibrosis using vitamin A‑coupled liposomes to deliver matrix metalloproteinase‑2 siRNA in vitro

  • Authors:
    • Yiping Li
    • Feng Liu
    • Fengan Ding
    • Pingsheng Chen
    • Meng Tang

  • View Affiliations

  • Published online on: May 25, 2015     https://doi.org/10.3892/mmr.2015.3842
  • Pages: 3453-3461

  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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 α‑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.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Journal Metrics
  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.647
  • SCImago Journal Rank (SJR): 0.781
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Spandidos Publications style
Li Y, Liu F, Ding F, Chen P and Tang M: Inhibition of liver fibrosis using vitamin A‑coupled liposomes to deliver matrix metalloproteinase‑2 siRNA in vitro. Mol Med Rep 12: 3453-3461, 2015.
APA
Li, Y., Liu, F., Ding, F., Chen, P., & Tang, M. (2015). Inhibition of liver fibrosis using vitamin A‑coupled liposomes to deliver matrix metalloproteinase‑2 siRNA in vitro. Molecular Medicine Reports, 12, 3453-3461. https://doi.org/10.3892/mmr.2015.3842
MLA
Li, Y., Liu, F., Ding, F., Chen, P., Tang, M."Inhibition of liver fibrosis using vitamin A‑coupled liposomes to deliver matrix metalloproteinase‑2 siRNA in vitro". Molecular Medicine Reports 12.3 (2015): 3453-3461.
Chicago
Li, Y., Liu, F., Ding, F., Chen, P., Tang, M."Inhibition of liver fibrosis using vitamin A‑coupled liposomes to deliver matrix metalloproteinase‑2 siRNA in vitro". Molecular Medicine Reports 12, no. 3 (2015): 3453-3461. https://doi.org/10.3892/mmr.2015.3842