title: Role of midkine-progranulin interaction during angiogenesis of hepatocellular carcinoma.
abstract: Midkine (MK) is a heparin-binding growth factor involved in growth, survival, migration, and differentiation of various target cells and dysregulation of MK signaling is implicated in a variety of inflammatory diseases and cancers. Although MK has been reported to act on endothelial cells and to have proangiogenic effects, the exact role of MK in angiogenesis is poorly defined. Progranulin (PGRN) is a secreted glycoprotein that functions as an important regulator of development, cell cycle progression, cell motility, tumorigenesis, angiogenesis. We screened the PGRN from the hepatic cancer cell cDNA library which was interacted with MK, and confirmed the binding by co-immunoprecipitation and co-localization. During our study, the interaction between MK and PGRN had the important role on the HUVECs proliferation, migration, and tubulogenesis, which indicated the interaction may regulate the angiogenesis, also the in vivo angiogenesis model CAM showed the promotion effect stimulated by MK and PGRN. These findings provide the first evidence linking the association of MK and PGRN and may identify the mechanism of MK during the hepatocellular carcinoma angiogenesis.
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Huang
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China ; Huzhou Teacher's Collage Huzhou 31300, Zhejiang Province, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Min
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Li
authors.affiliation: Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital Huzhou 31300, Zhejiang Province, China.
authors.forename: Licheng
authors.initials: L
authors.lastname: Dai
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply*; D000078792:Midkine; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D000077153:Progranulins; D015398:Signal Transduction / Q000502:physiology; D020798:Two-Hybrid System Techniques
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C066254:MDK protein, human; D009414:Nerve Growth Factors; D000077153:Progranulins; D000078792:Midkine
keywords: Midkine; angiogenesis; hepatocellular carcinoma; progranulin; protein-protein interaction