Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Sivak, Jeremy M.; West‐Mays, Judith A.; Yee, Amy S.; Williams, Trevor; Fini, M. Elizabeth

doi:10.1128/mcb.24.1.245-257.2004

Cited by 83 publications

(80 citation statements)

References 60 publications

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“…MMP9 plays a critical role in the development of tumor-associated vasculature and can enhance the invasive potential of tumor cells (Pepper, 2001;Hojilla et al, 2003). Upregulation of this gene may be linked to increased levels of HMGA1 and TFAP2A, which are both positive regulators of MMP9 (Liu et al, 1999;Sivak et al, 2004). In breast cancer patients, TFAP2A is highly associated with MMP9 expression (Pellikainen et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

et al. 2006

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“…The regulation of MMPs and TIMPs by the Hox and Pax families of developmental patterning genes has been little studied, although it is known that Pax6 binds the MMP9 promoter (Sivak et al, 2004) and BARX2 binds to the TIMP4 gene (Stevens et al, 2004). If BARX2 is an intrinsic regulator of MMP and TIMP genes, it might play a role in developmental patterning of the mammary gland.…”

Section: Discussionmentioning

confidence: 99%

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

Stevens

Meech

2006

Oncogene

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The estrogen receptor-a gene (ESR1) was previously identified as a direct target of the homeobox transcription factor BARX2 in MCF7 cells. Here, we show that BARX2 and ESR1 proteins bind to different ESR1 gene promoters and regulate the expression of alternatively spliced mRNAs that encode 66 and 46 kDa ESR1 protein isoforms. BARX2 increases the expression of both ESR1 isoforms; however, it has a greater effect on the 46 kDa isoform, leading to an increased ratio between the 46 and 66 kDa proteins. BARX2 also influences estrogen-dependent processes such as anchorage-independent growth and modulates the expression of the estrogen-responsive genes SOX5, RBM15, Dynein and Mortalin. In addition, BARX2 expression promotes cellular invasion and increases the expression of active matrix metalloproteinase-9 (MMP9). BARX2 also increases the expression of the tissue inhibitor of metalloproteinase (TIMP) genes, TIMP1 and TIMP3, in cooperation with estrogen signaling. Overall, these data indicate that BARX2 and ESR1 may coordinately regulate cell growth, survival and invasion pathways that are critical to breast cancer progression.

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“…In experimental corneal epithelial wounds, increased MMP-9 production has been observed in the basal corneal epithelial cells. 24,25 In contrast, increased MMP-9 has been observed in all layers of the corneal epithelium, including the superficial cells in inflammatory conditions, such as herpetic keratitis. 26 Therefore, MMP-9 may affect the superficial corneal epithelium either by direct production by these cells, or by paracellular diffusion from deeper epithelial layers, a process that can be enhanced by the epithelial stress of dry eye.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-9 Knockout Confers Resistance to Corneal Epithelial Barrier Disruption in Experimental Dry Eye

Pflugfelder

Farley

Luo

et al. 2005

The American Journal of Pathology

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277

239

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Altered corneal epithelial barrier function is the cause for ocular irritation and visual morbidity in dry eye disease. Increased matrix metalloproteinase (MMP)-9 activity has been observed in the tear fluid of dry eye patients. To determine the pathogenic role of MMP-9 in the corneal epithelial disease of dry eye, the effects of experimentally induced dry eye on corneal epithelial morphology and barrier function were compared in MMP-9 knockout mice and their wild-type littermates. Dry eye was created through cholinergic blockade and exposure to a desiccating environment. The tear fluid MMP-9 concentration increased in response to dryness in wild-type mice. Corneal epithelial permeability to three different-sized molecules increased in dry eye wild-type mice, but not in MMP-9 knockout mice. Topical administration of active MMP-9 to dry eye MMP-9 knockout mice significantly increased corneal epithelial permeability. Compared to MMP-9 knockout mice, wild-type mice showed greater desquamation of differentiated apical corneal epithelial cells that expressed the tight junction protein occludin in response to dryness. This was accompanied by an increase in lower sized (50 kd) occludin in the corneal epithelia of wild-type mice. These findings could be replicated in cultured human corneal epithelial cells that were treated with active MMP-9. These studies indicate that increased MMP-9 activity on the ocular surface in response to dryness disrupts corneal epithelial barrier function. This appears to be because Corneal epithelial disease, termed keratitis sicca, is a severe and sight-threatening complication of dry eye. 1 A key clinical feature of keratitis sicca is disruption of corneal epithelial barrier function. [2][3][4] This results in eye irritation, corneal surface irregularity, blurred and fluctuating vision, and increased risk for corneal ulceration. 4 -8 Ocular surface inflammation has been implicated in the pathogenesis of keratitis sicca. Elevated levels of proinflammatory cytokines, such as interleukin (IL)-1, have been detected in the tear fluid of patients with this condition. 9 -11 Furthermore, the concentration and activity of matrix metalloproteinase (MMP)-9 in the tear fluid was found to be significantly increased in these eyes, with the highest concentrations observed in eyes with the severe corneal epithelial disease or sterile corneal ulcers. 10 -12 We hypothesize that MMP-9 plays an important role in the disruption of corneal epithelial barrier function in dry eye. We previously reported an experimental murine model of dry eye that disrupts corneal epithelial barrier function similar to human dry eye disease. 13 The purpose of this study was to compare the effects of experimentally induced dry eye (EIDE) on corneal epithelial morphology and barrier function in MMP-9 knockout mice and their wild-type (WT) littermates. Materials and Methods MiceThis research protocol was approved by the Baylor College of Medicine Center for Comparative Medicine and it conformed to the standards in the Association...

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Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase B

Cited by 83 publications

References 60 publications

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

Matrix Metalloproteinase-9 Knockout Confers Resistance to Corneal Epithelial Barrier Disruption in Experimental Dry Eye

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