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Distribution of TGF-beta isoforms and signaling intermediates in corneal fibrotic wound repair.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2009 Oct 01; Vol. 108 (2), pp. 476-88. - Publication Year :
- 2009
-
Abstract
- In this study, temporal and spatial distribution of three TGF-beta isoforms and their downstream signaling pathways including pSmad2 and p38MAPK were examined during fibrotic wound repair. In normal chick corneas, TGF-beta1, -2, and -3 were weakly detected in Bowman's layer (BL). In healing corneas, TGF-beta1 was primarily deposited in the fibrin clot and the unwounded BL. TGF-beta2 was highly expressed in healing epithelial and endothelial cells, and numerous active fibroblasts/myofibroblasts. TGF-beta3 was mainly detected in the unwound region of basal epithelial cells. alpha-Smooth muscle actin (alpha-SMA) was initially appeared in the posterior region of repairing stroma at day 3, and was detected in the entire healing stroma by day 7. Notably, alpha-SMA was absent in the central region of healing stroma by day 14, and its staining pattern was similar to those of TGF-beta2 and p38MAPK. By contrast, pSmad2 was mainly detected in the fibroblasts. In normal cornea, laminin was mainly detected in both epithelial basement membrane (BM) and Descemet's membrane (DM). By contrast to reconstitution of the BM in the wound region, the DM was not repaired although endothelial layer was regenerated, indicating that high levels of TGF-beta2 were released into the posterior region of healing stroma on day 14. High levels of alpha-SMA staining, shown in cultured repair stromal cells from healing corneas on day 14 and in TGF-beta2 treated normal stromal cells, were significantly reduced by p38MAPK inhibition. Collectively, this study suggests that TGF-beta2-mediated myofibroblast transformation is mediated, at least partly, by the p38MAPK pathway in vivo.<br /> ((c) 2009 Wiley-Liss, Inc.)
- Subjects :
- Ablation Techniques
Actins metabolism
Aging
Animals
Basement Membrane metabolism
Bowman Membrane metabolism
Cells, Cultured
Chickens
Cornea pathology
Cornea surgery
Descemet Membrane metabolism
Fibrin metabolism
Fibrosis
Laminin metabolism
Protein Isoforms
Protein Serine-Threonine Kinases antagonists & inhibitors
Receptor, Transforming Growth Factor-beta Type I
Receptors, Transforming Growth Factor beta antagonists & inhibitors
Smad2 Protein metabolism
Stromal Cells metabolism
Stromal Cells pathology
Time Factors
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases metabolism
Corneal Injuries
Intracellular Signaling Peptides and Proteins metabolism
Transforming Growth Factor beta metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4644
- Volume :
- 108
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19626665
- Full Text :
- https://doi.org/10.1002/jcb.22277