Distribution of TGF-β isoforms and signaling intermediates in corneal fibrotic wound repair

Man Il Huh, Yeoun Hee Kim, Jong Hyuck Park, Sung Won Bae, Min Hee Kim, Yongmin Chang, Song Ja Kim, Sun Ryung Lee, Young Sup Lee, Eun Jung Jin, Jong Kyung Sonn, Shin Sung Kang, Jae Chang Jung

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

In this study, temporal and spatial distribution of three TGF-β isoforms and their downstream signaling pathways including pSmad2 and p38MAPK were examined during fibrotic wound repair. In normal chick corneas, TGF-β1, -2, and -3 were weakly detected in Bowman's layer (BL). In healing corneas, TGF-β1 was primarily deposited in the fibrin clot and the unwounded BL. TGF-β2 was highly expressed in healing epithelial and endothelial cells, and numerous active fibroblasts/myofibroblasts. TGF-β3 was mainly detected in the unwound region of basal epithelial cells. a-Smooth muscle actin (a-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, a-SMA was absent in the central region of healing stroma by day 14, and its staining pattern was similar to those of TGF-β2 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-β2 were released into the posterior region of healing stroma on day 14. High levels of a-SMA staining, shown in cultured repair stromal cells from healing corneas on day 14 and in TGF-β2 treated normal stromal cells, were significantly reduced by p38MAPK inhibition. Collectively, this study suggests that TGF-β2-mediated myofibroblast transformation is mediated, at least partly, by the p38MAPK pathway in vivo.

Original languageEnglish
Pages (from-to)476-488
Number of pages13
JournalJournal of Cellular Biochemistry
Volume108
Issue number2
DOIs
StatePublished - 1 Oct 2009

Keywords

  • α-SMA
  • Corneal wound healing
  • Fibrosis
  • p38MAPK
  • pSmad2
  • TGF-β

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