CTGF

CTGF, or connective tissue growth factor, also known as CCN2, is a secreted matricellular protein that belongs to the CCN family. It regulates processes such as cell adhesion, migration, proliferation, differentiation, and extracellular matrix production. CTGF expression is induced by growth factors like transforming growth factor-beta (TGF-β) and it plays roles in development, wound healing, and tissue repair. Dysregulated CTGF expression is linked to fibrotic diseases and cancer.

The CTGF/CCN2 gene encodes a protein of approximately 38–40 kDa that is secreted into the extracellular space. It contains four conserved modules: an IGF-binding protein–like domain, a von Willebrand factor type C–like domain, a thrombospondin type 1–like domain, and a C-terminal cystine knot domain. These modules enable CTGF to form multimers and to interact with extracellular matrix components such as collagens and fibronectin, as well as with cell surface receptors.

Mechanistically, CTGF acts as a signaling cofactor that modulates multiple pathways, including TGF-β, BMP, and integrin signaling. It can bind to integrins (for example, αvβ3 and α5β1) and heparan sulfate proteoglycans, influencing cell adhesion, migration, proliferation, and ECM synthesis. Its activity is context-dependent and can be shaped by mechanical cues in the cellular environment.

In physiology, CTGF contributes to embryonic development, angiogenesis, and wound healing. In pathology, overexpression or sustained activation promotes fibrotic diseases of the lung, liver, kidney, and skin, and it may support tumor progression through ECM remodeling and pro-angiogenic effects. Clinically, CTGF is explored as a biomarker and therapeutic target; anti-CTGF antibodies such as pamrevlumab (FG-3019) have been evaluated in trials for idiopathic pulmonary fibrosis, systemic sclerosis, and certain cancers.