title: Inhibition of liver fibrosis using vitamin A-coupled liposomes to deliver matrix metalloproteinase-2 siRNA in vitro.
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.
authors.affiliation: Department of Pathology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Fengan
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Pathology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Toxicology, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D055785:Gene Knockdown Techniques; D008081:Liposomes; D008103:Liver Cirrhosis / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats; D014162:Transfection; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D034741:RNA, Small Interfering; D014801:Vitamin A; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat