CTGF Biology
CTGF belongs to the CCN (CTGF/Cyr61/Cef10/NOVH) protein family, which is comprised of six secreted proteins that reside in the extracellular matrix (ECM). The ECM is a dynamic microenvironment surrounding cells that supports and affects cellular function and enables communication between cells. By modulating signals from a variety of molecules, CCN proteins play an important role in the ECM and influence a number of critical cellular processes as well as ECM homeostasis.
The diverse range of biological functions affected by CCN proteins is enabled by a unique multi-modular structure characteristic of the CCN family whereby each protein is comprised of four functional domains. Each domain can uniquely and specifically interact with ligands, such as growth factors, other ECM-associated proteins, and cell surface proteins. These interactions enable CTGF and other CCN proteins to influence cellular functions through modulation, potentiation and integration of ligand signals, signal cross-talk, and intracellular signaling pathways.
CTGF causes a variety of cellular responses including reduced cell adhesion and enhanced cell migration and proliferation. CTGF has also been shown to be essential for epithelial to mesenchymal transition (EMT), a process whereby normal functioning cells morph into ones that produce mainly scar tissue (of which collagen in the major protein component). Cellular responses to CTGF also have effects at the tissue level including remodeling, formation of new blood vessels (angiogenesis), changes in blood vessel architecture (permeability and stiffness), and replacement of normal tissue with scar tissue.
Nearly a decade of research conducted by FibroGen and others demonstrates the critical role of CTGF in all forms of chronic fibrotic disease whereby persistent and excessive scarring leads to organ dysfunction and failure. In chronic kidney disease, in which fibrosis underlies disease progression to end-stage renal disease, FibroGen is also focused on further understanding the role of CTGF in early-stage disease pathologies, such as proteinuria. FibroGen’s cancer program is exploring how CTGF-mediated processes, such as EMT, angiogenesis and cell adhesion, may promote tumor cell survival and metastasis in certain cancers.
CTGF is a protein comprised of four functional domains, each having the capacity to interact with multiple other biological ligands. These interactions can result in cellular responses that lead to tissue damage and loss of organ function in a variety of chronic diseases and may contribute to tumor cell survival and metastasis in certain cancers.
