AIM: To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)-induced liver fibrosis in rats. METHODS: Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wk via a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS: When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenic TGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col I, Col III, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10 vs. 14.16 ± 6.50, 2.02 ± 0.45 vs. 10.00 ± 3.35, 2.91 ± 0.30 vs. 7.83 ± 1.10, 4.64 ± 1.25 vs. 18.52 ± 7.61, 0.46 ± 0.16 vs. 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION: Infusion of exogenous AcSDKP attenuated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
AIM: To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)-induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wk via a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS: When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenic TGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col I, Col III, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10 vs. 14.16 ± 6.50, 2.02 ± 0.45 vs. 10.00 ± 3.35, 2.91 ± 0.30 vs. 7.83 ± 1.10, 4.64 ± 1.25 vs. 18.52 ± 7.61, 0.46 ± 0.16 vs. 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION: Infusion of exogenous AcSDKP attenuated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
Entities:
Keywords:
Bone morphological protein-7; Epithelial-mesenchymal transition; Fibroblast specific protein-1; Liver fibrosis; N-acetyl-seryl-aspartyl-lysyl-proline; Transformating growth factor-β1; α-smooth mucle actin
Authors: Jian-Miao Liu; Maria-Concepcion Garcia-Alvarez; Jerome Bignon; Michal Kusinski; Krzysztof Kuzdak; Andrew Riches; Joanna Wdzieczak-Bakala Journal: Ann N Y Acad Sci Date: 2010-04 Impact factor: 5.691
Authors: Saman Rasoul; Oscar A Carretero; Hongmei Peng; Maria A Cavasin; Jialong Zhuo; Alicia Sanchez-Mendoza; David R Brigstock; Nour-Eddine Rhaleb Journal: J Hypertens Date: 2004-03 Impact factor: 4.844
Authors: Ross G Douglas; Rajni K Sharma; Geoffrey Masuyer; Lizelle Lubbe; Ismael Zamora; K Ravi Acharya; Kelly Chibale; Edward D Sturrock Journal: Clin Sci (Lond) Date: 2014-02 Impact factor: 6.124
Authors: Jin Wang; Ye Qian; Xuemin Gao; Na Mao; Yucong Geng; Gaojie Lin; Guibin Zhang; Han Li; Fang Yang; Hong Xu Journal: Drug Des Devel Ther Date: 2020-10-19 Impact factor: 4.162