title: Notch Signaling Pathway Regulates Angiogenesis via Endothelial Cell in 3D Co-Culture Model.
abstract: This study aimed to investigate the role of Notch signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model with co-culture of adipose-derived stromal cells (ASCs) and endothelial cells (ECs). A 3D collagen gel model was established in vitro by implanting both ASCs from green fluorescent protein-labeled mouse and ECs from red fluorescent protein-labeled mouse, and the phenomena of angiogenesis with Notch signaling inducer Jagged1, inhibitor DAPT and PBS, respectively were observed by confocal laser scanning microscopy. Semi-quantitative PCR and immunofluorescent staining were conducted to detect expressions of angiogenesis-related genes and proteins. Angiogenesis in the co-culture gels was promoted by Jagged1 treatment while attenuated by DAPT treatment, compared to control group. In co-culture system of ASCs and ECs, the gene expressions of VEGFA, VEGFB, Notch1, Notch2, Hes1, Hey1, VEGFR1,and the protein expression of VEGFA, VEGFB, Notch1, Hes1, Hey1 were increased by Jagged1 treatment and decreased by DAPT treatment in ECs. And the result of VEGFR3 was the opposite. However, the same results did not appear completely in ASCs. These results revealed the VEGFA/B-Notch1/2-Hes1/Hey1- VEGFR1/3 signal axis played an important role in angiogenesis when ASCs and ECs were co-cultured in a 3D collagen gel model. J. Cell. Physiol. 232: 1548-1558, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Changyue
authors.initials: C
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Sirong
authors.initials: S
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Qianshun
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005782:Gels; D000072100:Jagged-1 Protein / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D051381:Rats; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D005782:Gels; D000072100:Jagged-1 Protein; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D040281:Vascular Endothelial Growth Factor Receptor-1