TITLE

Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expression data

AUTHOR(S)
Tong, Louis; Chew, Jaime; Yang, Henry; Ang, Leonard P. K.; Tan, Donald T. H.; Beuerman, Roger W.
PUB. DATE
January 2009
SOURCE
BMC Medical Genomics;2009, Vol. 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Pterygium is a common ocular surface disease characterized by fibrovascular invasion of the cornea and is sight-threatening due to astigmatism, tear film disturbance, or occlusion of the visual axis. However, the mechanisms for formation and post-surgical recurrence of pterygium are not understood, and a valid animal model does not exist. Here, we investigated the possible mechanisms of pterygium pathogenesis and recurrence. Methods: First we performed a genome wide expression analysis (human Affymetrix Genechip, >22000 genes) with principal component analysis and clustering techniques, and validated expression of key molecules with PCR. The controls for this study were the un-involved conjunctival tissue of the same eye obtained during the surgical resection of the lesions. Interesting molecules were further investigated with immunohistochemistry, Western blots, and comparison with tear proteins from pterygium patients. Results: Principal component analysis in pterygium indicated a signature of matrix-related structural proteins, including fibronectin-1 (both splice-forms), collagen-1A2, keratin-12 and small proline rich protein-1. Immunofluorescence showed strong expression of keratin-6A in all layers, especially the superficial layers, of pterygium epithelium, but absent in the control, with up-regulation and nuclear accumulation of the cell adhesion molecule CD24 in the pterygium epithelium. Western blot shows increased protein expression of beta-microseminoprotein, a protein up-regulated in human cutaneous squamous cell carcinoma. Gene products of 22 up-regulated genes in pterygium have also been found by us in human tears using nano-electrospray-liquid chromatography/mass spectrometry after pterygium surgery. Recurrent disease was associated with up-regulation of sialophorin, a negative regulator of cell adhesion, and never in mitosis a-5, known to be involved in cell motility. Conclusion: Aberrant wound healing is therefore a key process in this disease, and strategies in wound remodeling may be appropriate in halting pterygium or its recurrence. For patients demonstrating a profile of 'recurrence', it may be necessary to manage as a poorer prognostic case and perhaps, more adjunctive treatment after resection of the primary lesion.
ACCESSION #
42309200

 

Related Articles

  • Normal Wound Healing in Mice Deficient for Fibulin-5, an Elastin Binding Protein Essential for Dermal Elastic Fiber Assembly. Qian Zheng; Jiwon Choi; Rouleau, Leonie; Leask, Richard L.; Richardson, James A.; Davis, Elaine C.; Yanagisawa, Hiromi // Journal of Investigative Dermatology;Dec2006, Vol. 126 Issue 12, p2707 

    Extracellular matrix proteins play a critical role in dermal wound healing by mediating matrix–cell interactions and re-establishing the dermal architecture and environment. Fibulin-5 is an elastin-binding protein essential for elastic fiber development in vivo, and it has recently been...

  • Effect of collagen cross-linking inhibition by local application of beta-aminopropionitrile fumarate on wound contraction and healing (macroscopic study). Sardari, Kamran; Sharifi, Siavash // Comparative Clinical Pathology;Aug2008, Vol. 17 Issue 3, p179 

    Wound contraction is a major component of second-intention wound healing. The mechanism of this process is not completely understood. Two theories have been described for the mechanism of the wound contraction. To evaluate the collagen cross-linking inhibition on wound contraction, the present...

  • Calcium-Based Nanoparticles Accelerate Skin Wound Healing. Kawai, Kenichiro; Larson, Barrett J.; Ishise, Hisako; Carre, Antoine Lyonel; Nishimoto, Soh; Longaker, Michael; Lorenz, H. Peter // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    Introduction: Nanoparticles (NPs) are small entities that consist of a hydroxyapatite core, which can bind ions, proteins, and other organic molecules from the surrounding environment. These small conglomerations can influence environmental calcium levels and have the potential to modulate...

  • The Spatial and Temporal Expression Patterns of Integrinα9β1 and One of Its Ligands, the EIIIA Segment of Fibronectin, in Cutaneous Wound Healing. Singh, Purva; Reimer, Corinne L.; Peters, John H.; Stepp, Mary Ann; Hynes, Richard O.; Van De Water, Livingston // Journal of Investigative Dermatology;Dec2004, Vol. 123 Issue 6, p1176 

    The fibronectins (FN) comprise a family of adhesive extracellular matrix proteins thought to mediate important functions in cutaneous wounds. Plasma fibronectin (pFN) extravasates for days from intact hyperpermeable vessels following injury whereas mRNAs encoding the cellular fibronectins (cFN)...

  • Role of oxygen in wound healing. Bishop, A. // Journal of Wound Care;Sep2008, Vol. 17 Issue 9, p399 

    Acute wounds are initially hypoxic. This state triggers the diffusion of oxygenated plasma from the surrounding intact tissue to the hypoxic area, and sets in train processes resulting in oxidative killing, angiogenesis and collagen synthesis.

  • Expression of Osteopontin in oesophageal squamous cell carcinoma. Kita, Y.; Natsugoe, S.; Okumura, H.; Matsumoto, M.; Uchikado, Y.; Setoyama, T.; Owaki, T.; Ishigami, S.; Aikou, T. // British Journal of Cancer;9/4/2006, Vol. 95 Issue 5, p634 

    Osteopontin is a multifunctional 34 kDa extracellular matrix protein with a cell-binding domain. It is involved cell adhesion and cell migration and is therefore considered to influence tumorigenesis and/or metastasis. The purpose of the present study was to evaluate the clinical significance of...

  • TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients. Pajares, M J; Agorreta, J; Salvo, E; Behrens, C; Wistuba, I I; Montuenga, L M; Pio, R; Rouzaut, A // British Journal of Cancer;3/11/2014, Vol. 110 Issue 6, p1545 

    Background:Transforming growth factor β-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small...

  • Overexpression of MMP-2 and MMP-9 in squamous cell carcinomas of immunosuppressed patients. Chebassier, N.; Leroy, S.; Tenaud, I.; Knol, A. C.; Dreno, B. // Archives of Dermatological Research;Mar2002, Vol. 294 Issue 3, p124 

    Investigates the role of matrix metalloproteinases (MMP) in the development of squamous cell carcinoma (SCC) in immunosuppressed patient. Description and function of MMP; Detection on the level of protein expression in the epidermis close to the tumor proliferation of immunosuppressed and...

  • Involvement of p53 and p16 Tumor Suppressor Genes in Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma. Arbiser, Jack L.; Fan, Chun-Yang; Su, Xiaobo; Van Emburgh, Beth O.; Cerimele, Francesca; Miller, Mark Steven; Harvell, Jeff; Marinkovich, M. Peter // Journal of Investigative Dermatology;Oct2004, Vol. 123 Issue 4, p788 

    Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive disorder characterized by the loss of collagen type VII, an intrinsic component of the anchoring fibrils, which attach the epidermis to the dermis. Of the genetic blistering disorders, RDEB has the highest rate of...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics