The inhibitory effect of ginsan on TGF-β mediated fibrotic process.

Abstract

Transforming growth factor-beta (TGF-β) plays a central role in the development of fibrosis by stimulating extracellular matrix accumulation, and signals either directly or indirectly through types I, II, and III (TβRI, II, and III) TGF-β receptor complexes. Ginsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. Here, we examine whether ginsan regulates the fibrogenic process by interfering with TGF-β signaling pathways. TGF-β treatment of murine or human normal lung fibroblasts enhanced the levels of several fibrotic markers, including smooth muscle alpha actin (α-SMA), collagen-1, and fibronectin. Interestingly, ginsan treatment either before or after TGF-β administration led to significant reductions in all of α-SMA, collagen-1, and fibronectin expression levels. Ginsan not only inhibited phosphorylation of Smad2 and Smad3, but also attenuated pERK and pAKT signaling induced by TGF-β. Moreover, ginsan restored TβRIII protein expression, which was significantly downregulated by TGF-β, but reduced TβRI and TβRII protein levels. In a murine model of bleomycin (BLM)-induced pulmonary fibrosis, ginsan significantly suppressed accumulation of collagen, α-SMA, and TGF-β. These data collectively suggest that ginsan acts as an effective anti-fibrotic agent in the treatment of pulmonary fibrosis by blocking multiple TGF-β signaling pathways.

• Authors: Ji-Yeon Ahn, Mi-Hyoung Kim, Min-Jin Lim, Sarah Park, Sae-lo-oom Lee, Yeon-Sook Yun, Jie-Young Song
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 226 Issue 5 Pg. 1241-7 (May 2011) ISSN: 1097-4652 [Electronic] United States
• PMID: 20945375 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Chemical References

• Actins
• Collagen Type I
• Fibronectins
• Polysaccharides
• Proteoglycans
• Receptors, Transforming Growth Factor beta
• Recombinant Proteins
• Smad2 Protein
• Smad3 Protein
• TGFB1 protein, human
• Transforming Growth Factor beta1
• ginsan
• Bleomycin
• betaglycan
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Actins (metabolism)
• Animals
• Bleomycin
• Collagen Type I (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (drug effects, metabolism, pathology)
• Fibronectins (metabolism)
• Fibrosis
• Genes, Reporter
• Humans
• Lung (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Phosphorylation
• Polysaccharides (pharmacology)
• Protein Serine-Threonine Kinases (drug effects, metabolism)
• Proteoglycans (drug effects, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pulmonary Fibrosis (chemically induced, metabolism, pathology, prevention & control)
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (drug effects, metabolism)
• Recombinant Proteins (metabolism)
• Signal Transduction (drug effects)
• Smad2 Protein (genetics, metabolism)
• Smad3 Protein (genetics, metabolism)
• Time Factors
• Transfection
• Transforming Growth Factor beta1 (metabolism)