CTGF

Connective tissue growth factor
Identifiers
Symbols	CTGF ; CCN2; HCS24; IGFBP8; NOV2
External IDs	OMIM: 121009 MGI: 95537 HomoloGene: 1431 GeneCards: CTGF Gene
Gene ontology Molecular function • fibronectin binding • integrin binding • protein binding • insulin-like growth factor binding • protein C-terminus binding • growth factor activity • heparin binding Cellular component • extracellular region • proteinaceous extracellular matrix • extracellular space • Golgi apparatus • cis-Golgi network • cytosol • plasma membrane • cell cortex • intracellular membrane-bounded organelle • perinuclear region of cytoplasm Biological process • cartilage condensation • ossification • angiogenesis • regulation of cell growth • tissue homeostasis • transcription initiation from RNA polymerase II promoter • cell adhesion • cell-matrix adhesion • signal transduction • integrin-mediated signaling pathway • cell-cell signaling • positive regulation of cell proliferation • fibroblast growth factor receptor signaling pathway • epidermis development • response to wounding • response to glucose • organ senescence • gene expression • positive regulation of gene expression • negative regulation of gene expression • cell migration • cell differentiation • lung development • regulation of chondrocyte differentiation • response to estradiol • positive regulation of collagen biosynthetic process • response to anoxia • intracellular signal transduction • chondrocyte proliferation • response to amino acid • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • response to peptide hormone • cellular lipid metabolic process • small molecule metabolic process • positive regulation of cell differentiation • positive regulation of JNK cascade • positive regulation of cell activation • response to mineralocorticoid • positive regulation of stress fiber assembly • cytosolic calcium ion transport • positive regulation of cardiac muscle contraction • negative regulation of cell death • extracellular matrix constituent secretion • positive regulation of G0 to G1 transition • positive regulation of ERK1 and ERK2 cascade • response to fatty acid • DNA biosynthetic process • reactive oxygen species metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1490	14219
Ensembl	ENSG00000118523	ENSMUSG00000019997
UniProt	P29279	P29268
RefSeq (mRNA)	NM_001901	NM_010217
RefSeq (protein)	NP_001892	NP_034347
Location (UCSC)	Chr 6: 131.95 – 131.95 Mb	Chr 10: 24.6 – 24.6 Mb
PubMed search	[1]	[2]

CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein). CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.

Structure and binding partners

Members of the CCN protein family, including CTGF, are structurally characterized by having four conserved, cysteine-rich domains. These domains are, from N- to C-termini, the insulin-like growth factor binding protein (IGFBP) domain, the von Willebrand type C repeats (vWC) domain, the thrombospondin type 1 repeat (TSR) domain, and a C-terminal domain (CT) with a cysteine knot motif. CTGF exerts its functions by binding to various cell surface receptors in a context-dependent manner, including integrin receptors, cell surface heparan sulfate proteoglycans (HSPGs), LRPs, and TrkA. In addition, CTGF also binds growth factors and extracellular matrix proteins. The N-terminal half of CTGF interacts with aggrecan, the TSR domain interacts with VEGF, and the CT domain interacts with members of the TGF-β superfamily, fibronectin, perlecan, fibulin-1, slit, and mucins.

Role in development

Knockout mice with the Ctgf gene disrupted die at birth due to respiratory stress as a result of severe chondrodysplasia. Ctgf-null mice also show defects in angiogenesis, with impaired interaction between endothelial cells and pericytes and collagen IV deficiency in the endothelial basement membrane. CTGF is also important for pancreatic beta cell development, and is critical for normal ovarian follicle development and ovulation.

Clinical significance

CTGF is associated with wound healing and virtually all fibrotic pathology. It is thought that CTGF can cooperate with TGF-β to induce sustained fibrosis and to exacerbate extracellular matrix production in association other fibrosis-inducing conditions. Overexpression of CTGF in fibroblasts promotes fibrosis in the dermis, kidney, and lung, and deletion of Ctgf in fibroblasts and smooth muscle cells greatly reduces bleomycin-induced skin fibrosis.

In addition to fibrosis, aberrant CTGF expression is also associated with many types of malignancies, diabetic nephropathy and retinopathy, arthritis, and cardiovascular diseases. Several clinical trials are now ongoing that investigate the therapeutic value of targeting CTGF in fibrosis, diabetic nephropathy, and pancreatic cancer.

See also

• Ctgf/hcs24 CAESAR
• CYR61 (CCN1)