WNT1-inducible-signaling pathway protein 1

WISP1
Identifiers
Aliases	WISP1, CCN4, WISP1c, WISP1i, WISP1tc, WNT1 inducible signaling pathway protein 1
External IDs	MGI: 1197008 HomoloGene: 2883 GeneCards: WISP1
Gene ontology Molecular function • integrin binding • heparin binding • insulin-like growth factor binding Cellular component • extracellular region • proteinaceous extracellular matrix • extracellular fluid • cytoplasm Biological process • Wnt signaling pathway • regulation of cell growth • cell adhesion • signal transduction • negative regulation of cell death • cell-cell signaling Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8840	22402
Ensembl	ENSG00000104415	ENSMUSG00000005124
UniProt	O95388	O54775
RefSeq (mRNA)	NM_001204869 NM_001204870 NM_003882 NM_080838	NM_018865
RefSeq (protein)	NP_001191798.1 NP_001191799.1 NP_003873.1 NP_543028.1	NP_061353.1
Location (UCSC)	Chr 8: 133.19 – 133.23 Mb	Chr 15: 66.89 – 66.92 Mb
PubMed search	[1]	[2]
Wikidata

WNT1-inducible-signaling pathway protein 1 (WISP-1),^[3] also known as CCN4, is a matricellular protein that in humans is encoded by the WISP1 gene.^[4][5]

Structure

WISP-1 is highly homologous to CYR61 (CCN1) and CTGF (CCN2), and is a member of the CCN family of secreted, extracellular matrix (ECM)-associated signaling proteins (CCN intercellular signaling protein). The CCN family of proteins shares a common molecular protein structure, characterized by an N-terminal secretory signal peptide followed by four distinct domains with homologies to insulin-like growth factor binding protein (IGFBP), von Willebrand type C repeats (vWC), thrombospondin type 1 repeat (TSR), and a cysteine knot motif within the C-terminal (CT) domain. This family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, differentiation, and survival.^[3][6][7][8]

Role in bone development

WISP-1 promotes mesenchymal cell proliferation and osteoblastic differentiation, and represses chondrocytic differentiation.^[9] WISP-1 binds BMP2 and enhances BMP2 function in osteogenesis.^[10] These activities may be modulated by its direct binding to decorin and biglycan,^[11] two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue.

Clinical significance

WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase,^[12] and inhibits TNF-induced cell death in cardiomyocytes.^[13] Recombinant WISP-1 enhances ECM deposition in human fibroblasts, suggesting that it might play a role in matrix remodeling in vivo. WISP-1 is upregulated in human patients with idiopathic pulmonary fibrosis and in a mouse model of bleomycin-induced lung fibrosis.^[14] Orotracheal application of WISP-1 neutralizing antibodies to the lung ameliorates bleomycin-induced lung fibrosis,^[14] raising the possibility that WISP-1 might be a potential target for anti-fibrotic therapy.^[3]

Expression of WISP-1 promotes tumor growth,^[15] and high WISP-1 expression correlates with advanced tumors of the brain, breast, colon, and lung.^{[16][17][18][19]} WISP-1 appears to inhibit metastasis^[20][21] although expression of a WISP-1 splicing variant lacking the VWC domain appears to enhance the invasive characteristic of gastric carcinoma cells.^[22]

References