Vatalanib, a tyrosine kinase inhibitor, decreases hepatic fibrosis and sinusoidal capillarization in CCl4-induced fibrotic mice
| Autor: | Liao‑Liao Zhao, Hao Li, Ya‑Ju Du, Ling‑Jian Kong, Jing Chen, Ying Hu, Feng‑Hua Pei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Liver Cirrhosis
Male Cancer Research Pathology medicine.medical_specialty Vatalanib hepatic sinusoidal cell capillarization medicine.drug_class Pyridines Biology Lung injury Biochemistry Tyrosine-kinase inhibitor 03 medical and health sciences chemistry.chemical_compound Hydroxyproline Mice 0302 clinical medicine Sinusoid Genetics medicine Animals hepatic fibrosis Molecular Biology Liver injury Mice Inbred BALB C vascular endothelial growth factor Carbon Tetrachloride Poisoning Articles medicine.disease Vascular endothelial growth factor Oncology chemistry 030220 oncology & carcinogenesis Molecular Medicine carbon tetrachloride vatalanib Phthalazines 030211 gastroenterology & hepatology Hepatic fibrosis |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Among the various consequence arising from lung injury, hepatic fibrosis is the most severe. Decreasing the effects of hepatic fibrosis remains one of the primary therapeutic challenges in hepatology. Dysfunction of hepatic sinusoidal endothelial cells is considered to be one of the initial events that occur in liver injury. Vascular endothelial growth factor signaling is involved in the progression of genotype changes. The aim of the present study was to determine the effect of the tyrosine kinase inhibitor, vatalanib, on hepatic fibrosis and hepatic sinusoidal capillarization in a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis. Liver fibrosis was induced in BALB/c mice using CCl4 by intraperitoneal injection for 6 weeks. The four experimental groups included a control, and three experimental groups involving administration of CCl4, vatalanib and a combination of the two. Histopathological staining and measuring live hydroxyproline content evaluated the extent of liver fibrosis. The expression of α-smooth muscle actin (SMA) and cluster of differentiation (CD) 34 was detected by immunohistochemistry. Collagen type I, α-SMA, transforming growth factor (TGF)-β1 and vascular endothelial growth factor receptor (VEGFR) expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Liver fibrosis scores and hydroxyproline content were decreased in both vatalanib groups. In addition, both doses of vatalanib decreased mRNA expression levels of hepatic α-SMA, TGF-β1, collagen-1, VEGFR1, and VEGFR2. Levels of α-SMA and CD34 protein were decreased in the vatalanib group compared with the CCl4 group. There were significant differences in the number of fenestrae per sinusoid between the groups. The present study identified that administration of vatalanib was associated with decreased liver fibrosis and hepatic sinusoidal capillarization in CCl4-induced mouse models, and is a potential compound for counteracting liver fibrosis. |
| Databáze: | OpenAIRE |
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