Abstract
This study aimed to investigate the effect of bile duct-targeting lecithins- (PC-) coupled decorin (DCN) (PC-DCN) nanoliposomes against liver fibrosis in vitro and in vivo. We prepared PC-DCN nanoliposomes by using rat astrocytes, HSC-T6, to verify the antifibrosis effect of PC-DCN in vitro. First, we established a rat model of carbon tetrachloride-induced fibrosis. PC-DCN nanoliposomes were then injected into fibrotic rats via the portal vein or bile duct. The EdU assay was performed to analyze cell proliferation. Immunofluorescence staining was used to detect α-smooth muscle actin (α-SMA) expression. Western blot was performed to examine the expression of α-SMA, collagen type I alpha 1 (COL1A1), and transforming growth factor-β (TGF-β) protein. The levels of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TBIL) were examined by enzyme-linked immunosorbent assay (ELISA) analysis. Hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to determine liver tissue lesions and liver fibrosis. Compared with TGF-β group, PC-DCN treatment could significantly reduce cell proliferation. Western blot analysis indicated that the expression of α-SMA, COL1A1, and TGF-β was downregulated after treatment with PC-DCN in vitro and in vivo. Immunofluorescence staining confirmed that α-SMA expression was reduced by PC-DCN. Furthermore, H&E staining and Masson trichrome staining showed that the administration of PC-DCN nanoliposomes via the bile duct could reduce the extent of liver fibrosis. PCR analysis showed that PC-DCN administration could reduce proinflammatory cytokines IL-6, TNF-α, and IL-1β expression via the bile duct. The administration of PC-DCN nanoliposomes also significantly downregulated liver function indicators ALT, AST, and TBIL. The results of our study indicated that PC-DCN could effectively reduce the extent of liver fibrosis.
Highlights
Liver fibrosis has become one of the common diseases threatening human health and largely affects the quality of life of the affected patients [1]
We found that DCN could relieve liver fibrosis following chronic carbon tetrachloride- (CCl4-) induced liver injury [9]
Immunofluorescence analysis was performed to detect the expression of α-smooth muscle actin (α-SMA) in fibrotic liver, the results showed that the expression of α-SMA fluorescence after PC-DCN treatment was downregulated in comparison with that in the transforming growth factor-β (TGF-β) group (Figure 2(d))
Summary
Liver fibrosis has become one of the common diseases threatening human health and largely affects the quality of life of the affected patients [1]. It progresses to irreversible liver cirrhosis, even liver cancer, if not diagnosed in a timely manner or if effective treatments are lacking [2]. Liver fibrosis is mainly caused by the excessive deposition of extracellular matrix (ECM) [3]. The excessive deposition of ECM, especially collagen fibrils, leads to the breakdown of the balance between synthesis and degradation, resulting in the loss of regeneration ability [4]. It is imperative to explore the mechanism underlying the development of liver fibrosis and search for effective treatment methods
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