title: Comparison of TGF-β, PDGF, and CTGF in hepatic fibrosis models using DMN, CCl4, and TAA.
abstract: Three chemotoxins including dimethylnitrosamine (DMN), carbon tetrachloride (CCl4), and thioacetamide (TAA) are commonly used in hepatofibrotic models. We aimed to draw characteristics of histopathology and pro-fibrogenic cytokines including TGF-β, PDGF and CTGF among three models. Rats were divided into six groups and intra-peritoneally injected with DMN (10 mg/kg, for three weeks, three consecutive days weekly), CCl4 (1.6 g/kg, for 10 weeks, twice weekly), TAA (200 mg/kg, for 12 weeks, twice weekly) or their corresponded treatment for each control group. The liver weights were decreased in DMN model, but not other models. Ascites were occurred as 3-, 2-, and 7-rats in DMN, CCl4, and TAA model, respectively. The lipid peroxidation was highest in CCl4 model, serum levels of liver enzymes were increased as similar severity. The hepatofibrotic alterations were remarkable in DMN and TAA model, but not CCl4 as evidenced by the Masson trichrome staining and hydroxyproline. The immunohistochemistry for α-SAM showed that the DMN model was most severely enhanced than other models. On the other hand, hepatic tissue levels of pro-fibrogenic cytokines including TGF-β, PDGF, and CTGF were generally increased in three models, but totally different among models or measurement resources. Especially, serum levels of three cytokines were remarkably increased by CCl4 injection and CTGF levels in both hepatic tissue and serum were highest in CCl4 group. Our results firstly demonstrated comparative study for features of morphological finding and pro-fibrogenic cytokines in serum and hepatic protein levels among three models. Above results would be a helpful reference for hepatofibrotic studies.
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Hyeong-Geug
authors.initials: HG
authors.lastname: Kim
authors.affiliation: b Laboratory of Medical Science , Dongguk University Medical Center, Dongguk University , Republic of Korea.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Choi
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Han
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: a Department of Liver and Immunology Research Center , Daejeon Oriental Hospital of Daejeon University , Republic of Korea and.
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D013853:Thioacetamide; D055513:Connective Tissue Growth Factor; D002251:Carbon Tetrachloride; D004128:Dimethylnitrosamine
keywords: Animal models; CTGF; PDGF-β; TGF-β; chemotoxins; liver fibrosis