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The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy.
Invest Ophthalmol Vis Sci. 2007 Sep; 48(9):4291-9.IO

Abstract

PURPOSE

Proliferative vitreoretinopathy (PVR), a major reason for failure of retinal detachment surgery, is characterized by the formation of scarlike tissue that contains transdifferentiated retinal pigment epithelial (RPE) cells. The scar tissue occurs in response to growth factors such as transforming growth factor (TGF)-beta and epidermal growth factor (EGF). The authors postulate that transdifferentiation of RPE cells may arise via epithelial-to-mesenchymal transition (EMT). Bone morphogenetic proteins (BMPs) are expressed in the retina and have an antiproliferative role. Gremlin is expressed in the outer retina and is a BMP antagonist. The study was conducted to establish a model of PVR by inducing EMT in the human RPE cell line ARPE-19, using TGF-beta and EGF and to establish the contribution of gremlin to EMT.

METHODS

ARPE-19 cells were cultured and stimulated with TGF-beta1, EGF, and gremlin. The expression of alpha-smooth muscle actin (alpha-SMA), vimentin, and zona occludens (ZO)-1 were examined via PCR, Western blot analysis, and immunofluorescence. Zymography was performed for matrix metalloproteinase (MMP) activity. Scratch assays were performed to assess migration.

RESULTS

A model of EMT was established in the ARPE-19 cell line. The characteristics of EMT include gain of alpha-SMA, loss of ZO-1, upregulation of MMP activity and enhanced migration. Gremlin plays an important role in this process, contributing to the gain of alpha-SMA, loss of ZO-1, and upregulation of MMP activity.

CONCLUSIONS

EMT occurs in vitro in the ARPE-19 cell line in response to the growth factors TGF-beta1 and EGF. EMT is also induced by Gremlin.

Authors+Show Affiliations

Department of Ophthalmology, Mater Misericordiae Hospital, University College Dublin, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17724219

Citation

Lee, Helena, et al. "The Role of Gremlin, a BMP Antagonist, and Epithelial-to-mesenchymal Transition in Proliferative Vitreoretinopathy." Investigative Ophthalmology & Visual Science, vol. 48, no. 9, 2007, pp. 4291-9.
Lee H, O'Meara SJ, O'Brien C, et al. The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2007;48(9):4291-9.
Lee, H., O'Meara, S. J., O'Brien, C., & Kane, R. (2007). The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy. Investigative Ophthalmology & Visual Science, 48(9), 4291-9.
Lee H, et al. The Role of Gremlin, a BMP Antagonist, and Epithelial-to-mesenchymal Transition in Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2007;48(9):4291-9. PubMed PMID: 17724219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy. AU - Lee,Helena, AU - O'Meara,Sarah J, AU - O'Brien,Colm, AU - Kane,Rosemary, PY - 2007/8/29/pubmed PY - 2007/10/12/medline PY - 2007/8/29/entrez SP - 4291 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 48 IS - 9 N2 - PURPOSE: Proliferative vitreoretinopathy (PVR), a major reason for failure of retinal detachment surgery, is characterized by the formation of scarlike tissue that contains transdifferentiated retinal pigment epithelial (RPE) cells. The scar tissue occurs in response to growth factors such as transforming growth factor (TGF)-beta and epidermal growth factor (EGF). The authors postulate that transdifferentiation of RPE cells may arise via epithelial-to-mesenchymal transition (EMT). Bone morphogenetic proteins (BMPs) are expressed in the retina and have an antiproliferative role. Gremlin is expressed in the outer retina and is a BMP antagonist. The study was conducted to establish a model of PVR by inducing EMT in the human RPE cell line ARPE-19, using TGF-beta and EGF and to establish the contribution of gremlin to EMT. METHODS: ARPE-19 cells were cultured and stimulated with TGF-beta1, EGF, and gremlin. The expression of alpha-smooth muscle actin (alpha-SMA), vimentin, and zona occludens (ZO)-1 were examined via PCR, Western blot analysis, and immunofluorescence. Zymography was performed for matrix metalloproteinase (MMP) activity. Scratch assays were performed to assess migration. RESULTS: A model of EMT was established in the ARPE-19 cell line. The characteristics of EMT include gain of alpha-SMA, loss of ZO-1, upregulation of MMP activity and enhanced migration. Gremlin plays an important role in this process, contributing to the gain of alpha-SMA, loss of ZO-1, and upregulation of MMP activity. CONCLUSIONS: EMT occurs in vitro in the ARPE-19 cell line in response to the growth factors TGF-beta1 and EGF. EMT is also induced by Gremlin. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/17724219/The_role_of_gremlin_a_BMP_antagonist_and_epithelial_to_mesenchymal_transition_in_proliferative_vitreoretinopathy_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.07-0086 DB - PRIME DP - Unbound Medicine ER -