Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

M Kolko; J F Kiilgaard; J Wang; K A Poulsen; J R Andreasen; M la Cour; M H Nissen; S Heegaard; N G Bazan; J U Prause; M Kolko; J F Kiilgaard; J Wang; K A Poulsen; J R Andreasen; M la Cour; M H Nissen; S Heegaard; N G Bazan; J U Prause

doi:10.1016/j.exer.2009.04.002

Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

M Kolko, J F Kiilgaard, J Wang, K A Poulsen, J R Andreasen, M la Cour, M H Nissen, S Heegaard, N G Bazan, J U Prause, M Kolko, J F Kiilgaard, J Wang, K A Poulsen, J R Andreasen, M la Cour, M H Nissen, S Heegaard, N G Bazan, J U Prause

8 Citations (Scopus)

Abstract

Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used to explore this role in vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA2-VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of proliferation, whereas over expression of iPLA2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.

Original language	English
Journal	Experimental Eye Research
Volume	89
Issue number	3
Pages (from-to)	383-91
Number of pages	9
ISSN	0014-4835
DOIs	https://doi.org/10.1016/j.exer.2009.04.002 https://doi.org/10.1016/j.exer.2009.04.002
Publication status	Published - 1 Sept 2009

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Kolko, M., Kiilgaard, J. F., Wang, J., Poulsen, K. A., Andreasen, J. R., la Cour, M., Nissen, M. H., Heegaard, S., Bazan, N. G., Prause, J. U., Kolko, M., Kiilgaard, J. F., Wang, J., Poulsen, K. A., Andreasen, J. R., la Cour, M., Nissen, M. H., Heegaard, S., Bazan, N. G., & Prause, J. U. (2009). Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases. Experimental Eye Research, 89(3), 383-91. https://doi.org/10.1016/j.exer.2009.04.002, https://doi.org/10.1016/j.exer.2009.04.002

Kolko, M , Kiilgaard, JF, Wang, J, Poulsen, KA, Andreasen, JR, la Cour, M, Nissen, MH, Heegaard, S, Bazan, NG, Prause, JU, Kolko, M, Kiilgaard, JF, Wang, J, Poulsen, KA, Andreasen, JR, la Cour, M, Nissen, MH, Heegaard, S, Bazan, NG & Prause, JU 2009, 'Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases', Experimental Eye Research, vol. 89, no. 3, pp. 383-91. https://doi.org/10.1016/j.exer.2009.04.002, https://doi.org/10.1016/j.exer.2009.04.002

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title = "Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases",

abstract = "Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used to explore this role in vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA2-VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of proliferation, whereas over expression of iPLA2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.",

author = "M Kolko and Kiilgaard, {J F} and J Wang and Poulsen, {K A} and Andreasen, {J R} and {la Cour}, M and Nissen, {M H} and S Heegaard and Bazan, {N G} and Prause, {J U} and M Kolko and Kiilgaard, {J F} and J Wang and Poulsen, {K A} and Andreasen, {J R} and {la Cour}, M and Nissen, {M H} and S Heegaard and Bazan, {N G} and Prause, {J U}",

note = "Keywords: Alternative Splicing; Animals; Cell Nucleus; Cell Proliferation; Cells, Cultured; Endoplasmic Reticulum; Gene Silencing; Humans; Phospholipases A2, Calcium-Independent; RNA, Small Interfering; Retinal Pigment Epithelium; Sus scrofa; Vitreoretinopathy, Proliferative",

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doi = "10.1016/j.exer.2009.04.002",

language = "English",

volume = "89",

pages = "383--91",

journal = "Experimental Eye Research",

issn = "0014-4835",

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T1 - Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

AU - Kolko, M

AU - Kiilgaard, J F

AU - Wang, J

AU - Poulsen, K A

AU - Andreasen, J R

AU - la Cour, M

AU - Nissen, M H

AU - Heegaard, S

AU - Bazan, N G

AU - Prause, J U

AU - Kolko, M

AU - Kiilgaard, J F

AU - Wang, J

AU - Poulsen, K A

AU - Andreasen, J R

AU - la Cour, M

AU - Nissen, M H

AU - Heegaard, S

AU - Bazan, N G

AU - Prause, J U

N1 - Keywords: Alternative Splicing; Animals; Cell Nucleus; Cell Proliferation; Cells, Cultured; Endoplasmic Reticulum; Gene Silencing; Humans; Phospholipases A2, Calcium-Independent; RNA, Small Interfering; Retinal Pigment Epithelium; Sus scrofa; Vitreoretinopathy, Proliferative

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used to explore this role in vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA2-VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of proliferation, whereas over expression of iPLA2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.

AB - Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used to explore this role in vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA2-VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of proliferation, whereas over expression of iPLA2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.

U2 - 10.1016/j.exer.2009.04.002

DO - 10.1016/j.exer.2009.04.002

M3 - Journal article

C2 - 19379734

SN - 0014-4835

VL - 89

SP - 383

EP - 391

JO - Experimental Eye Research

JF - Experimental Eye Research

IS - 3

ER -

Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

Abstract

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