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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 is essential for persistent fibrosis. One day old neonatal mice were injected SC daily for 7 days with 800 ng TGFβ2 alone or with 400 ng CTGF. FG-3019 was also administered to one group that received CTGF. The injections were then stopped for 4 days and the mice were sacrificed to examine the deposition of ECM components and cellular invasion. Panel A: the experimental design. Panel B: A cross section of the skin, SC space and underlying muscle from representative mice is shown. The arrows point out fibrotic response to the various treatments.
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Figure 3: CTGF is essential for persistent fibrosis. One day old neonatal mice were injected SC daily for 7 days with 800 ng TGFβ2 alone or with 400 ng CTGF. FG-3019 was also administered to one group that received CTGF. The injections were then stopped for 4 days and the mice were sacrificed to examine the deposition of ECM components and cellular invasion. Panel A: the experimental design. Panel B: A cross section of the skin, SC space and underlying muscle from representative mice is shown. The arrows point out fibrotic response to the various treatments.

Mentions: In 1999, Mori et al. reported that CTGF was required to observe persistent fibrosis after injection of TGFβ into rodents [33]. We and others have been able to confirm their observations in several different experimental models, including one that closely resembles the experiment they performed (Figure 3). One day old neonatal mice were injected subcutaneously in the scapular region daily for 7 days with TGFβ2 or TGFβ2 plus CTGF. The mice were then maintained for another 4 days until they were sacrificed and examined for deposition of ECM and cellular infiltration. As pointed out by the arrows in Figure 3 (panel B), TGFβ induced a modest fibrotic response while that induced by the combination of TGFβ plus CTGF was obviously greater. Co-injection of FG-3019 with the TGFβ and CTGF suppressed all of the response to the presence of CTGF, demonstrating that the antibody was capable of completely inhibiting the biological activity 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 is essential for persistent fibrosis. One day old neonatal mice were injected SC daily for 7 days with 800 ng TGFβ2 alone or with 400 ng CTGF. FG-3019 was also administered to one group that received CTGF. The injections were then stopped for 4 days and the mice were sacrificed to examine the deposition of ECM components and cellular invasion. Panel A: the experimental design. Panel B: A cross section of the skin, SC space and underlying muscle from representative mice is shown. The arrows point out fibrotic response to the various treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: CTGF is essential for persistent fibrosis. One day old neonatal mice were injected SC daily for 7 days with 800 ng TGFβ2 alone or with 400 ng CTGF. FG-3019 was also administered to one group that received CTGF. The injections were then stopped for 4 days and the mice were sacrificed to examine the deposition of ECM components and cellular invasion. Panel A: the experimental design. Panel B: A cross section of the skin, SC space and underlying muscle from representative mice is shown. The arrows point out fibrotic response to the various treatments.
Mentions: In 1999, Mori et al. reported that CTGF was required to observe persistent fibrosis after injection of TGFβ into rodents [33]. We and others have been able to confirm their observations in several different experimental models, including one that closely resembles the experiment they performed (Figure 3). One day old neonatal mice were injected subcutaneously in the scapular region daily for 7 days with TGFβ2 or TGFβ2 plus CTGF. The mice were then maintained for another 4 days until they were sacrificed and examined for deposition of ECM and cellular infiltration. As pointed out by the arrows in Figure 3 (panel B), TGFβ induced a modest fibrotic response while that induced by the combination of TGFβ plus CTGF was obviously greater. Co-injection of FG-3019 with the TGFβ and CTGF suppressed all of the response to the presence of CTGF, demonstrating that the antibody was capable of completely inhibiting the biological activity 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