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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Mol Med Rep. 2015 Sep ;12(3):3453-61. Epub 2015 May 25. PMID: 26017616

Abstract Author(s):

Yiping Li, Feng Liu, Fengan Ding, Pingsheng Chen, Meng Tang

Article Affiliation:

Yiping Li

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 presentstudy 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 inchronic liver disease.

Study Type : In Vitro Study

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Sayer Ji
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