| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Departments of Ophthalmology and 2Pathology, Wakayama Medical University, Wakayama, Japan; the 3Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida; and the 4Department of Ophthalmology, University of Cincinnati Medical Center, Cincinnati, Ohio.
PURPOSE. The purpose of the present study was to examine the roles of signaling pathways potentially activated by TGFß (i.e., Smad and p38 mitogen-activated kinase [MAPK]) in regulation of cell migration and proliferation of healing mouse corneal epithelium.
METHODS. Activation of Smads or p38MAPK was evaluated by immunohistochemistry in healing mouse corneal epithelium after debridement. The role of endogenous TGFß or p38MAPK in epithelial healing was determined in organ-cultured mouse corneas with an epithelial defect, in the presence or absence of a TGFß-neutralizing antibody or p38MAPK inhibitors, respectively. Cell proliferation was evaluated by incorporation of bromodeoxyuridine.
RESULTS. Migrating mouse corneal epithelium had minimal cell proliferation. Smad3 and -4 were found in nuclei of normal corneal epithelium, whereas they were absent in nuclei of migrating cells in association with Smad7 upregulation on epithelial debridement. Administration of TGFß-neutralizing antibody reduced the protein expression of Smad7 in vivo after a corneal injury. In contrast, phosphorylation and nuclear translocation of p38MAPK were markedly evident in migrating epithelium during healing, but not in uninjured epithelium. In organ culture, addition of p38MAPK inhibitors blocked cell migration more markedly than neutralizing TGFß-antibody and enhanced cell proliferation in the injured corneal epithelium, in association with phosphorylation of Erk.
CONCLUSIONS. Endogenous TGFß 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.
This article has been cited by other articles:
|
|
 |
|
  K.-i. Miyazaki, Y. Okada, O. Yamanaka, A. Kitano, K. Ikeda, S. Kon, T. Uede, S. R. Rittling, D. T. Denhardt, W. W.-Y. Kao, et al. Corneal Wound Healing in an Osteopontin-Deficient Mouse Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1367 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kimura, S. Teranishi, J. Yamauchi, and T. Nishida Role of JNK-Dependent Serine Phosphorylation of Paxillin in Migration of Corneal Epithelial Cells during Wound Closure Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Zaniolo, M.-E. Gingras, M. Audette, and S. L. Guerin Expression of the Gene Encoding Poly(ADP-ribose) Polymerase-1 Is Modulated by Fibronectin during Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4199 - 4210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Levin and A. S. Verkman Aquaporin-3-Dependent Cell Migration and Proliferation during Corneal Re-epithelialization. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4365 - 4372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, H. He, C.-L. Kuo, Y. Gao, T. Kawakita, and S. C. G. Tseng Basement membrane dissolution and reassembly by limbal corneal epithelial cells expanded on amniotic membrane. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2381 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saika, K. Ikeda, O. Yamanaka, K. C. Flanders, Y. Okada, T. Miyamoto, A. Kitano, A. Ooshima, Y. Nakajima, Y. Ohnishi, et al. Loss of Tumor Necrosis Factor {alpha} Potentiates Transforming Growth Factor {beta}-mediated Pathogenic Tissue Response during Wound Healing Am. J. Pathol., June 1, 2006; 168(6): 1848 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Lee, J. H. Lee, M. Kim, Y. Kariya, K. Miyazaki, and E. K. Kim Insulin-like Growth Factor-1 Induces Migration and Expression of Laminin-5 in Cultured Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 873 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. He, H.-T. Cho, W. Li, T. Kawakita, L. Jong, and S. C. G. Tseng Signaling-Transduction Pathways Required for Ex Vivo Expansion of Human Limbal Explants on Intact Amniotic Membrane Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 151 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Harper, S. M. Alvares, and W. G. Carter Wounding activates p38 map kinase and activation transcription factor 3 in leading keratinocytes J. Cell Sci., August 1, 2005; 118(15): 3471 - 3485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. K. Hutcheon, X. Q. Guo, M. A. Stepp, K. J. Simon, P. H. Weinreb, S. M. Violette, and J. D. Zieske Effect of Wound Type on Smad 2 and 4 Translocation Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2362 - 2368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, T. Miyamoto, O. Yamanaka, T. Kato, Y. Ohnishi, K. C. Flanders, K. Ikeda, Y. Nakajima, W. W.-Y. Kao, M. Sato, et al. Therapeutic Effect of Topical Administration of SN50, an Inhibitor of Nuclear Factor-{kappa}B, in Treatment of Corneal Alkali Burns in Mice Am. J. Pathol., May 1, 2005; 166(5): 1393 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, K. Ikeda, O. Yamanaka, T. Miyamoto, Y. Ohnishi, M. Sato, Y. Muragaki, A. Ooshima, Y. Nakajima, W. W.-Y. Kao, et al. Expression of Smad7 in Mouse Eyes Accelerates Healing of Corneal Tissue after Exposure to Alkali Am. J. Pathol., May 1, 2005; 166(5): 1405 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Kim, L. Luo, S. C. Pflugfelder, and D.-Q. Li Doxycycline Inhibits TGF-{beta}1-Induced MMP-9 via Smad and MAPK Pathways in Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 840 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Y. Rhyu, Y. Yang, H. Ha, G. T. Lee, J. S. Song, S.-t. Uh, and H. B. Lee Role of Reactive Oxygen Species in TGF-{beta}1-Induced Mitogen-Activated Protein Kinase Activation and Epithelial-Mesenchymal Transition in Renal Tubular Epithelial Cells J. Am. Soc. Nephrol., March 1, 2005; 16(3): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Chwieralski, I. Schnurra, L. Thim, and W. Hoffmann Epidermal Growth Factor and Trefoil Factor Family 2 Synergistically Trigger Chemotaxis on BEAS-2B Cells via Different Signaling Cascades Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 528 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Frey, A. Golovin, and D. B. Polk Epidermal Growth Factor-stimulated Intestinal Epithelial Cell Migration Requires Src Family Kinase-dependent p38 MAPK Signaling J. Biol. Chem., October 22, 2004; 279(43): 44513 - 44521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, Y. Muragaki, Y. Okada, T. Miyamoto, Y. Ohnishi, A. Ooshima, and W. W.-Y. Kao Sonic Hedgehog Expression and Role in Healing Corneal Epithelium Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2577 - 2585. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
