title: Role of CCN5 (WNT1 inducible signaling pathway protein 2) in pancreatic islets.
abstract: In search of direct targets of insulin-like growth factor (IGF)-1 action, we discovered CCN5 (WNT1 inducible signaling pathway protein 2 [WISP2]) as a novel protein expressed in pancreatic β-cells. As a member of the "CCN" ( C ysteine-rich angiogenic inducer 61 [Cyr61], C onnective tissue growth factor [CTGF in humans], and N ephroblastoma overexpressed [Nov; in chickens]) family, the expression of CCN5/WISP2 is stimulated by IGF-1 together with Wnt signaling. When overexpressed in insulinoma cells, CCN5 promotes cell proliferation and cell survival against streptozotocin-induced cell death. The cell proliferation effect seems to be caused by AKT phosphorylation and increased cyclin D1 levels. These properties resemble those of CCN2/CTGF, another isoform of the CCN family, although CCN5 is the only one within the family of six proteins that lacks the C-terminal repeat. Treatment of primary mouse islets with recombinant CCN5 protein produced similar effects to those of gene transfection, indicating that either as a matricellular protein or a secreted growth factor, CCN5 stimulates β-cell proliferation and regeneration in a paracrine fashion. This review also discusses the regulation of CCN5/WISP2 by estrogen and its involvement in angiogenesis and tumorigenesis.
authors.affiliation: Fraser Laboratories, Department of Medicine, The Research Institute of McGill University Health Centre, Montreal, Canada.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Fraser Laboratories, Department of Medicine, The Research Institute of McGill University Health Centre, Montreal, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Kaddour
authors.affiliation: Fraser Laboratories, Department of Medicine, The Research Institute of McGill University Health Centre, Montreal, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Fraser Laboratories, Department of Medicine, The Research Institute of McGill University Health Centre, Montreal, Canada.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, The Research Institute of McGill University Health Centre, Montreal, Canada.
authors.forename: Zu-Hua
authors.initials: ZH
authors.lastname: Gao
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C413323:CCN5 protein, human; D012097:Repressor Proteins; D007334:Insulin-Like Growth Factor I
keywords: Wnt signal; Wnt信号; cyclin D1; insulin-like growth factor-1; matricellular protein; proliferation; 细胞周期蛋白D1; 细胞基质蛋白; 细胞增殖; 胰岛素样生长因子甲