Role of p38 MAP Kinase in Regulation of Cell Migration and Proliferation in Healing Corneal Epithelium

Abstract

Endogenous TGFbeta enhances migration of corneal epithelium during wound healing in mice. The p38MAPK, but not the Smad, cascade plays a major role in promoting cell migration and in suppressing cell proliferation in migrating epithelium.

Role of Reactive Oxygen Species in TGF-β1-Induced Mitogen-Activated Protein Kinase Activation and Epithelial-Mesenchymal Transition in Renal Tubular Epithelial Cells

“…ERK activation is also required in TGF-␤1-induced EMT in pancreatic cancer cells (20) and mammary epithelial cells (21). Activation of p38 MAPK is required in TGF-␤1-induced EMT in mammary epithelial cells (22) and in migration and proliferation of healing corneal epithelium (23). In agreement with these observations, our data also suggest that both p38 MAPK and ERK are required in TGF-␤1-induced EMT in NRK-52E cells.…”

“…In a normal rat tubular epithelial cell line NRK-52E, Li et al (15) showed that TGF-␤1 induced Smad 2 phosphorylation and resulted in the transformation of epithelial cell into myofibroblast phenotype with the loss of E-cadherin and de novo expression of ␣-SMA and collagens I, III, and IV and that overexpression of Smad 7 resulted in marked inhibition of TGF-␤-induced Smad 2 activation with the prevention of EMT and collagen synthesis. In addition to Smad pathway, Rho A (16,17) and mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinases (ERK) (18 -21), p38 MAPK (22,23), and c-Jun N-terminal kinases (JNK) (24) are involved in TGF-␤1-induced EMT. There is a cross-talk between ERK and Smad 2 (10,25).…”

Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice

“…TGF-b modulates behaviors of several corneal cell types, that is, epithelial cell migration and proliferation and transdifferentiation of keratocytes to myofibroblasts, and also is chemotactic to monocytes/macrophages during wound healing in the cornea as in other tissues. [12][13][14] Blocking signaling mediated by Smad2/3, the cytoplasmic signaling intermediates specific for TGF-b/ activin, is effective in inhibiting injury-induced tissue fibrosis in many tissues, such as skin, kidney, and the lens and retina of the eye. [15][16][17][18][19][20][21][22][23][24][25][26] We have recently revealed that both topical administration of SN50, an inhibitor of NF-kB signal, and adenoviral gene introduction of the Smad7, an inhibitory Smad that blocks Smads2/3, block tissue destruction in an alkali-burned cornea in mice (Saika et al, 2004 24,35 ).…”

Inhibition of p38MAP kinase suppresses fibrotic reaction of retinal pigment epithelial cells

“…[21][22][23][24][25][26][27] We and others have also recently reported that the TGF-b2/ p38MAPK cascade, which is activated in mouse corneal epithelium upon epithelial debridement, is needed for epithelial cell migration and cessation of cell proliferation. 28,29 In mesenchymal cells, p38MAPK is involved in expression of ECM molecules, that is, collagen or fibronectin and cell proliferation. 30,31 While not yet proven, these observations suggest that the p38MAPK pathway might be involved in the pathogenesis of tissue fibrosis, as in PVR.…”