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CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis.

Lipson KE, Wong C, Teng Y, Spong S - Fibrogenesis Tissue Repair (2012)

Bottom Line: A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications.FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model.When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased.

View Article: PubMed Central - HTML - PubMed

Affiliation: FibroGen, Inc., 409 Illinois St., San Francisco, CA 94158, USA.

ABSTRACT
CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis.

No MeSH data available.


Related in: MedlinePlus

CTGF affects multiple signaling pathways and processes important in pathophysiology. CTGF interacts with a variety of molecules, including cytokines and growth factors, receptors and matrix proteins. These interactions alter signal transduction pathways, either positively or negatively, which results in changes in cellular responses.
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Figure 1: CTGF affects multiple signaling pathways and processes important in pathophysiology. CTGF interacts with a variety of molecules, including cytokines and growth factors, receptors and matrix proteins. These interactions alter signal transduction pathways, either positively or negatively, which results in changes in cellular responses.

Mentions: CTGF has been reported to interact with a variety of molecules after being secreted from cells (Figure 1). Some of the molecules with which CTGF has been reported to interact are cytokines and growth factors such as IGF1, BMP4, BMP7, TGFβ, and VEGF. Other molecules are cell surface receptors with other known ligands such as TrkA, LRP1, LRP6 and several different integrins. CTGF has also been reported to interact with matrix proteins such as fibronectin or heparan sulfate proteoglycans (HSPGs) that may be in the matrix or on the cell surface. Interaction with each of these various molecules has been reported to be dependent on the different domains of CTGF.


CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis.

Lipson KE, Wong C, Teng Y, Spong S - Fibrogenesis Tissue Repair (2012)

CTGF affects multiple signaling pathways and processes important in pathophysiology. CTGF interacts with a variety of molecules, including cytokines and growth factors, receptors and matrix proteins. These interactions alter signal transduction pathways, either positively or negatively, which results in changes in cellular responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368796&req=5

Figure 1: CTGF affects multiple signaling pathways and processes important in pathophysiology. CTGF interacts with a variety of molecules, including cytokines and growth factors, receptors and matrix proteins. These interactions alter signal transduction pathways, either positively or negatively, which results in changes in cellular responses.
Mentions: CTGF has been reported to interact with a variety of molecules after being secreted from cells (Figure 1). Some of the molecules with which CTGF has been reported to interact are cytokines and growth factors such as IGF1, BMP4, BMP7, TGFβ, and VEGF. Other molecules are cell surface receptors with other known ligands such as TrkA, LRP1, LRP6 and several different integrins. CTGF has also been reported to interact with matrix proteins such as fibronectin or heparan sulfate proteoglycans (HSPGs) that may be in the matrix or on the cell surface. Interaction with each of these various molecules has been reported to be dependent on the different domains of CTGF.

Bottom Line: A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications.FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model.When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased.

View Article: PubMed Central - HTML - PubMed

Affiliation: FibroGen, Inc., 409 Illinois St., San Francisco, CA 94158, USA.

ABSTRACT
CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis.

No MeSH data available.


Related in: MedlinePlus