title: Collagen-binding vascular endothelial growth factor attenuates CCl4-induced liver fibrosis in mice.
abstract: Vascular endothelial growth factor (VEGF) serves an important role in promoting angiogenesis and tissue regeneration. However, the lack of an effective delivery system that can target this growth factor to the injured site reduces its therapeutic efficacy. Therefore, in the current study, collagen‑binding VEGF was constructed by fusing a collagen‑binding domain (CBD) to the N‑terminal of native VEGF. The CBD‑VEGF can specifically bind to collagen which is the major component of the extracellular matrix in fibrotic liver. The anti‑fibrotic effects of this novel material were investigated by the carbon tetrachloride (CCl4)‑induced liver fibrotic mouse model. Mice were injected with CCl4 intraperitoneally to induce liver fibrosis. CBD‑VEGF was injected directly into the liver tissue of mice. The liver tissues were stained with hematoxylin and eosin for general observation or with Masson's trichrome staining for detection of collagen deposition. The hepatic stellate cell activation, blood vessel formation and hepatocyte proliferation were measured by immunohistochemical staining for α‑smooth muscle actin, CD31 and Ki67 in the liver tissue. The fluorescent TUNEL assay was performed to evaluate the hepatocyte apoptosis. The present study identified that the CBD‑VEGF injection could significantly promote vascularization of the liver tissue of fibrotic mice and attenuate liver fibrosis. Furthermore, hepatocyte apoptosis and hepatic stellate cell activation were attenuated by CBD‑VEGF treatment. CBD‑VEGF treatment could additionally promote hepatocyte regeneration in the liver tissue of fibrotic mice. Thus, it was suggested that CBD‑VEGF may be used as a novel therapeutic intervention for liver fibrosis.
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Cao
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: DaI
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology* / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D002251:Carbon Tetrachloride