Connective Tissue Growth Factor or CTGF is a protein of the extracellular matrix variety. Also known as CCN2, this matricellular protein is part of the CNN group. Connective Tissue growth factor has a number of different roles in various processes in the body including but not limited to proliferation, skeletal development and the healing of wounds as well as tissue repair. It is also implicated in many other processes including osteogenesis, angiogenesis and chondrogenesis. CTGF also plays a crucial role in various forms of cancer.
Structure OF CTGF
CTGF is rich in cysteine and has four modules that make up the extracellular matrix protein. The domains or modules can be divided into the domain that holds the growth factor protein that is similar to insulin, a C-terminal domain that has a cysteine knot, a domain for thrombospondin type 1 and the vWC domain or Von Willebrand type C.
The CTGF uses its functions by using cell surface receptors and binding with them in a way that is completely context dependant. This does include LRPs, integrin receptors and HSPGs or heparan sulphate proteoglycan.
As well as this, CTGF may also bind extracellular matrix proteins together with growth factors. For this, the CTGF is divided. One part of the CTGF or the N-terminal domain forms with aggrecan. On the other side, the TSR domain meshes with VEGF while members of the TGF family, mucins, perlecan and fibulin interact with the CT domain of the protein.
Function Of CTGF
Studies on mice have found that CTGF has a number of significant impacts on growth and development. One study revealed that if the CTGF gene is impacted, then mice died at birth. This was due to respiratory stress and was caused by chondrodysplasia.
As well as this, mice without the CTGF were also found to have severe defects for angiogenesis. It effected how endothelial cells interacted with pericytes. There was also evidence of a collagen IV deficiency as the point of the endothelial basement membrane. Further studies have also revealed that the protein is important for the development of the pancreatic beta cell. Furthermore, evidence has shown that it is crucial for normal ovulation.
Further research on mice has demonstrated that the CTGF also impacts the maintenance and indeed the development of cellular tissues. Nul CTGF mice were shown to suffer from skeletal dysmorphisms due to a damaged growth plate angiogenesis as well as issues with mineralization.
As CTGF is linked to any fibrotic pathology researchers, have explored and investigated targeting CTGF and the medical value that this could bring. These have included research studies into everything from pancreatic cancer to typical fibrosis. As well as being associated with wound healing CTGF is hypothesised to caused fibrosis that can be sustained. CTGF overexpression has already been shown to encourage fibrosis in the lung and kidney. Research is still ongoing into the impact this could have on certain diseases. However, with CTGF playing such a crucial role in key biological processes, there is reason to continue to evaluate its value for potential treatment.