1. Role of CCN5 ( WNT1 inducible signaling pathway protein 2) in pancreatic islets.
- Author
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Liu, Jun ‐ Li, Kaddour, Nancy, Chowdhury, Subrata, Li, Qing, and Gao, Zu ‐ hua
- Subjects
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CYCLINS , *SOMATOMEDIN C , *ISLANDS of Langerhans , *CELL proliferation , *WNT signal transduction - 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' ( Cysteine-rich angiogenic inducer 61 [ Cyr61], Connective tissue growth factor [ CTGF in humans], and Nephroblastoma 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. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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