title: Hydrodynamics-based transfection of rat interleukin-10 gene attenuates porcine serum-induced liver fibrosis in rats by inhibiting the activation of hepatic stellate cells.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Yun-Xin
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D015316:Genetic Therapy; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D057446:Hydrodynamics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000503:physiopathology / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism*; D014162:Transfection
chemical_list: D000199:Actins; D003094:Collagen; D016753:Interleukin-10; D012333:RNA, Messenger; C498862:Acta2 protein, rat