Increased expression of gelatinase (MMP-2 and MMP-9) in pterygia and pterygium fibroblasts with disease progression and activation of protein kinase C.

PURPOSE To study the expression of matrix metalloprotease (MMP)-2 and MMP-9 mRNA and activities in various stages of surgically excised pterygium specimens and cultured pterygium fibroblasts and to study the effects of activation of protein kinase C (PKC) on the expression of these MMPs in pterygium fibroblasts. METHODS MMP-2 and MMP-9 mRNA expression and activities in 15 pterygium tissues and cultured pterygium fibroblasts were measured by RT-PCR and zymography. Five normal conjunctiva specimens and fibroblasts were tested as the controls. Changes of expression of MMP-2 and MMP-9 of fibroblasts after the simulation of a standard PKC activator, 2-O-tetradecanoyl-phorbol-13-acetate (TPA), were studied. RESULTS MMP-2 and MMP-9 expression in pterygium tissues and fibroblasts was greater than those of normal tissues and fibroblasts and was closely relevant to the progression of pterygium. In early-stage pterygium tissues and cultured fibroblasts, MMP-9 was not expressed, activated MMP-2 could not be detected, and only a small amount of latent MMP-2 was present. In advanced-stage pterygium (pterygium head passed the papillary region), MMP-9 was expressed; activated MMP-2 and a large amount of latent MMP-2 could be detected in pterygium tissues and fibroblasts. TPA stimulated the expression of MMP-2 and MMP-9 by pterygium fibroblasts isolated from early-stage specimens in a dose-dependent manner. CONCLUSIONS MMP-2 and MMP-9 expression by pterygium fibroblasts is significantly increased after the progression of pterygium. Activation of the PKC signaling pathway, aside from other previously reported signaling pathways, may play a role in the development and progression of pterygium.

[1]  P. Wang,et al.  Clinical significance of matrix metalloproteinase-2 in cancer of uterine cervix: a semiquantitative study of immunoreactivities using tissue array. , 2008, Gynecologic oncology.

[2]  G. Yen,et al.  Lucidenic acid inhibits PMA-induced invasion of human hepatoma cells through inactivating MAPK/ERK signal transduction pathway and reducing binding activities of NF-kappaB and AP-1. , 2007, Carcinogenesis.

[3]  D. Wakefield,et al.  Epidermal growth factor receptor signaling is partially responsible for the increased matrix metalloproteinase-1 expression in ocular epithelial cells after UVB radiation. , 2005, The American journal of pathology.

[4]  G. Sethi,et al.  Role of protein kinase Cδ in UV-B-induced apoptosis of macrophages in vitro , 2005 .

[5]  Yu-Ying He,et al.  Delayed and Sustained Activation of Extracellular Signal-regulated Kinase in Human Keratinocytes by UVA , 2004, Journal of Biological Chemistry.

[6]  Xiangping Liu,et al.  [Expression of matrix metalloproteinase in human pterygia]. , 2004, Yan ke xue bao = Eye science.

[7]  D. Hu,et al.  Uveal melanocytes produce matrix metalloproteinases-2 and -9 in vitro. , 2004, Pigment cell research.

[8]  D. Wakefield,et al.  Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases , 2004, Progress in Retinal and Eye Research.

[9]  D. Wakefield,et al.  UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. , 2003, Investigative ophthalmology & visual science.

[10]  J. Cheong,et al.  Induction of matrix metalloproteinase‐9 (MMP‐9) in lipopolysaccharide‐stimulated primary astrocytes is mediated by extracellular signal‐regulated protein kinase 1/2 (Erk1/2) , 2003, Glia.

[11]  C. Rhee,et al.  Modulation of phorbol ester-induced regulation of matrix metalloproteinases and tissue inhibitors of metalloproteinases by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase. , 2002, Journal of neurosurgery.

[12]  D. Wakefield,et al.  Active matrilysin (MMP-7) in human pterygia: potential role in angiogenesis. , 2001, Investigative ophthalmology & visual science.

[13]  T. Shearer,et al.  Activation of extracellular signal-regulated kinase in trabecular meshwork cells. , 2001, Experimental eye research.

[14]  G. Schultz,et al.  Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing altered limbal epithelial basal cells. , 2001, Archives of ophthalmology.

[15]  D. Wakefield,et al.  Differential expression of matrix metalloproteinases and their tissue inhibitors at the advancing pterygium head. , 2000, Investigative ophthalmology & visual science.

[16]  S. Tseng,et al.  Regulation of collagenase, stromelysin, and urokinase-type plasminogen activator in primary pterygium body fibroblasts by inflammatory cytokines. , 2000, Investigative ophthalmology & visual science.

[17]  R. Rodnight,et al.  Protein Kinase C-Mediated in vitro Invasion of Human Glioma Cells through Extracellular-Signal-Regulated Kinase and Ornithine Decarboxylase , 2000, Pathobiology.

[18]  D. Wakefield,et al.  Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells. , 2000, Investigative ophthalmology & visual science.

[19]  D. English,et al.  Sun exposure and pterygium of the eye: a dose-response curve. , 1999, American journal of ophthalmology.

[20]  D. Wakefield,et al.  The pathogenesis of pterygia. , 1999, Current opinion in ophthalmology.

[21]  J. Westermarck,et al.  Regulation of matrix metalloproteinase expression in tumor invasion , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  G. Butler,et al.  Mechanisms for pro matrix metalloproteinase activation , 1999, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[23]  V. Kähäri,et al.  Role of thymic peptides as transmitters between the neuroendocrine and immune systems. , 1999 .

[24]  T. Amemiya,et al.  Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA analysis , 1998, Graefe's Archive for Clinical and Experimental Ophthalmology.

[25]  Voon Wee Yong,et al.  Matrix metalloproteinases and diseases of the CNS , 1998, Trends in Neurosciences.

[26]  P. Basset,et al.  Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. , 1997, Matrix biology : journal of the International Society for Matrix Biology.

[27]  G. Murphy,et al.  Relating matrix metalloproteinase structure to function: why the "hemopexin" domain? , 1997, Matrix biology : journal of the International Society for Matrix Biology.

[28]  D. Wakefield,et al.  Increased expression of matrix metalloproteinases in vivo in scleritis tissue and in vitro in cultured human scleral fibroblasts. , 1997, The American journal of pathology.

[29]  S. Zucker,et al.  Activation of human umbilical vein endothelial cell progelatinase A by phorbol myristate acetate: a protein kinase C-dependent mechanism involving a membrane-type matrix metalloproteinase. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[30]  S. Tseng,et al.  Three patterns of cytokine expression potentially involved in epithelial‐fibroblast interactions of human ocular surface , 1995, Journal of cellular physiology.

[31]  James P. Quigley,et al.  Matrix Metalloproteinase-2 Is an Interstitial Collagenase , 1995, The Journal of Biological Chemistry.

[32]  M. Matsubara,et al.  Unique regulation of the matrix metalloproteinase, gelatinase B. , 1995, Investigative ophthalmology & visual science.

[33]  R. Tsai,et al.  Fibroblasts isolated from human pterygia exhibit transformed cell characteristics , 1994, In Vitro Cellular & Developmental Biology - Animal.

[34]  A. M. Romanic,et al.  Extracellular Matrix‐Degrading Proteinases in the Nervous System , 1994, Brain pathology.

[35]  M. Coroneo Pterygium as an early indicator of ultraviolet insolation: a hypothesis. , 1993, The British journal of ophthalmology.

[36]  M. Fini,et al.  The pattern of metalloproteinase expression by corneal fibroblasts is altered by passage in cell culture. , 1990, Journal of cell science.

[37]  S. Horiguchi,et al.  Pterygium in welders. , 1984, The British journal of ophthalmology.

[38]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[39]  J H HILGERS,et al.  Pterygium: its incidence, heredity and etiology. , 1960, American journal of ophthalmology.

[40]  D. Wakefield,et al.  The pathogenesis of pterygium: current concepts and their therapeutic implications. , 2008, The ocular surface.

[41]  S. Tseng,et al.  Overexpression of collagenase (MMP-1) and stromelysin (MMP-3) by pterygium head fibroblasts. , 2001, Archives of ophthalmology.

[42]  L. Coussens,et al.  Matrix metalloproteinases and the development of cancer. , 1996, Chemistry & biology.

[43]  Y. Okada,et al.  Localization of matrix metalloproteinase 9 (92-kilodalton gelatinase/type IV collagenase = gelatinase B) in osteoclasts: implications for bone resorption. , 1995, Laboratory investigation; a journal of technical methods and pathology.