CTGF

CCN2
Identifiers
Aliases	CCN2, HCS24, IGFBP8, NOV2, connective tissue growth factor, cellular communication network factor 2, CTGF
External IDs	OMIM: 121009; MGI: 95537; HomoloGene: 1431; GeneCards: CCN2; OMA:CCN2 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q23.2 Start 131,948,176 bp[1] End 131,951,372 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 A4|10 11.84 cM Start 24,471,340 bp[2] End 24,474,581 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia thoracic aorta ascending aorta smooth muscle tissue gastric mucosa right coronary artery gallbladder Descending thoracic aorta left coronary artery tendon of biceps brachii Top expressed in tunica media of zone of aorta stroma of bone marrow ascending aorta semi-lunar valve ankle joint aortic valve skin of external ear ankle ciliary body epithelium of lens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function fibronectin binding insulin-like growth factor binding protein C-terminus binding protein binding growth factor activity integrin binding heparin binding Cellular component cytosol cis-Golgi network plasma membrane extracellular region cell cortex perinuclear region of cytoplasm extracellular space extracellular matrix collagen-containing extracellular matrix Biological process positive regulation of collagen biosynthetic process positive regulation of cell activation cell differentiation regulation of chondrocyte differentiation response to amino acid response to estradiol response to anoxia intracellular signal transduction response to mineralocorticoid response to fatty acid DNA biosynthetic process positive regulation of cell death ossification response to organic cyclic compound extracellular matrix constituent secretion lung development response to peptide hormone positive regulation of G0 to G1 transition positive regulation of JNK cascade response to glucose negative regulation of gene expression reactive oxygen species metabolic process fibroblast growth factor receptor signaling pathway positive regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of gene expression connective tissue development response to wounding regulation of cell growth angiogenesis tissue homeostasis positive regulation of cell population proliferation chondrocyte proliferation positive regulation of cell differentiation epidermis development positive regulation of cardiac muscle contraction positive regulation of ERK1 and ERK2 cascade positive regulation of protein phosphorylation integrin-mediated signaling pathway transcription initiation from RNA polymerase II promoter cell-matrix adhesion cell migration cartilage condensation positive regulation of stress fiber assembly human ageing cell adhesion cell-cell signaling negative regulation of cell death regulation of signaling receptor activity Sources:Amigo / QuickGO
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: 24.47 – 24.47 Mb PubMed search [3] [4]
Wikidata
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CTGF, also known as CCN2 or connective tissue growth factor,^[5][6] is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein).^[7][8][9] 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.^[5][6][10]

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,^[11][12][13] cell surface heparan sulfate proteoglycans (HSPGs),^[14] LRPs,^[15] and TrkA.^[16] In addition, CTGF also binds growth factors and extracellular matrix proteins. The N-terminal half of CTGF interacts with aggrecan,^[17] the TSR domain interacts with VEGF,^[18] and the CT domain interacts with members of the TGF-β superfamily, fibronectin, perlecan, fibulin-1, slit, and mucins.^[5][6]

Role in development

Knockout mice with the Ctgf gene disrupted die at birth due to respiratory stress as a result of severe chondrodysplasia.^[19] 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.^[20] CTGF is also important for pancreatic beta cell development,^[21] and is critical for normal ovarian follicle development and ovulation.^[22]

Clinical significance

CTGF is associated with wound healing and virtually all fibrotic pathology.^[9][23] It is thought that CTGF can cooperate with TGF-β to induce sustained fibrosis^[24] and to exacerbate extracellular matrix production in association other fibrosis-inducing conditions.^[23] Overexpression of CTGF in fibroblasts promotes fibrosis in the dermis, kidney, and lung,^[25] and deletion of Ctgf in fibroblasts and smooth muscle cells greatly reduces bleomycin-induced skin fibrosis.^[26]

In addition to fibrosis, aberrant CTGF expression is also associated with many types of malignancies, diabetic nephropathy^[27] 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.^[5]

CTGF (CCN2) has recently been implicated in mood disorders, notably in the postpartum period; these effects may be mediated by its effects on myelination ^[28]

See also

• Ctgf/hcs24 CAESAR
• CYR61 (CCN1)

References

External links

• Human CTGF genome location and CTGF gene details page in the UCSC Genome Browser.