Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells
| Autor: | Li-Juan Zhang, Zhi-Xin Chen, Yun-Xin Chen, Yue-Hong Huang, Xiao-Zhong Wang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
Male Serum medicine.medical_specialty Genetic enhancement interleukin-10 chemical and pharmacologic phenomena Biology Transfection Proinflammatory cytokine Rats Sprague-Dawley Liver Function Tests Fibrosis Internal medicine parasitic diseases Hepatic Stellate Cells Genetics medicine Animals RNA Messenger liver fibrosis hydrodynamics-based transfection medicine.diagnostic_test hemic and immune systems Genetic Therapy Articles General Medicine medicine.disease gene therapy co-culture Molecular biology Actins Coculture Techniques biological factors medicine.anatomical_structure Endocrinology Hepatocyte Hydrodynamics Hepatic stellate cell Collagen Liver function Liver function tests Plasmids |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2014.1831 |
| Popis: | Liver fibrosis is the common pathological outcome for the majority of chronic liver diseases. Interleukin-10 (IL-10) is a cytokine that downregulates proinflammatory responses and has a modulatory effect on liver fibrogenesis. However, little is known regarding the effect of rat interleukin-10 (rIL-10) gene by hydrodynamics-based transfection (HBT) on liver fibrosis in rats. The aim of this study was to investigate the effect of the rIL-10 gene by HBT on the progression of liver fibrosis induced by porcine serum (PS) in rats and explore its possible mechanism. Plasmid-expressing rIL-10 was transferred into rats by HBT and immunohistochemistry and RT-PCR were used to detect the major organ expressing rIL-10. Liver fibrosis was induced in rats by intraperitoneal administration of PS for 8 weeks. Plasmid pcDNA3-rIL-10 solution was administered weekly by HBT starting at the 5th week. Liver function and hepatic histology were examined. The possible molecular mechanisms of rIL-10 gene therapy were assessed in liver tissue and hepatic stellate cells (HSCs) co-cultured with BRL cells (a hepatocyte line) in vitro. The results showed rIL-10 expression occurred mainly in the liver following rIL-10 gene transfer by HBT. Maintaining a stable expression of rIL-10 in serum was assessed by repeated administration. The rIL-10 gene treatment attenuated liver inflammation and fibrosis in PS-induced fibrotic rats, reduced the deposition of collagen and the expression of α-smooth muscle actin (α-SMA) in fibrotic rats. The in vitro experiment showed that the expression of a-SMA and procollagen type I in HSCs co-cultured with the BRL-transfected rIL-10 gene were significantly decreased. These findings indicate that rIL-10 gene therapy by HBT attenuates PS-induced liver fibrosis in rats and that its mechanism is associated with rIL-10 inhibiting the activation of HSCs and promoting the degeneration of collagen. |
| Databáze: | OpenAIRE |
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