Expression of TGF-β superfamily receptors in the retinal pigmented epithelium

Mitsuhiro, M. R. K. H.; Ishida, K.; Shimizu, A.; Goto, D.; Yamashita, H.

doi:10.5935/0004-2749.19980071

SUMMARY

Background:

Retinal pigment epithelial (RPE) cells play an important role in the inflammatory response of the eye. Trans-forming growth factor-beta (TGF-β) and other members of the TGF-β superfamily are described to regulate some RPE cells functions. In this study the expression of TGF-β superfamily receptors in RPE cells at mRNA level was investigated

Methods:

RT-PCR technique was performed using mRNAs from D407 RPE cells (human RPE cell line) and HaCatTcells (human keratinocyte cell line used as positive control).

Results:

Expression of 6 type 1 receptors (TGF-β type I receptor, ALK-1, Activin type I receptor, activin type IB receptor, BMP type SA receptor, BMP type IB receptor), and 4 type II receptors (TGF-β type lI receptor, activin type II receptor, activin type IIB receptor, BMP type II receptor) were studied. The results demonstrated that TGF-β, activins and BMPs express their own specific receptors at mRNA level.

Conclusions:

The present study suggests that TGF-β superfamily members can exert effects on D407 RPE cells through their specific receptors.

Key words:
TGF-β superfamily receptor; Retinal pigment epithelial cells; Polymerase chain reaction

RESUMO

Objetivo:

O epitélio pigmentário da retina (EPR) desempenha um importante papel na resposta inflamatória ocular. "Transforming growth factor-beta" (TGF-β) e outros membros de sua superfamília têm sido descritos como reguladores de certas funções do EPR. Neste estudo, os autores investigaram a expressão de receptores da superfamília de TGF-β superfamily nas células do EPR a nível de RNA mensageiro.

Métodos:

Técnica de RT-PCR foi usada com RNA mensageiro de D407 (linhagem de células do EPR humano) e HaCatT (linhagem de queratócitos humanos usados como controle positivo).

Resultados:

A expressão de 6 receptores tipo I (TGF-β receptor tipo I, ALK-I, activina receptor tipo I, activina receptor tipo IB, BMP receptor tipo IA, BMP receptor tipo IB), e 4 receptores tipo II (TGF-β receptor tipo II, activina receptor tipo II, activina receptor tipo IIB, BMP receptor tipo II) foi investigada. Os resultados demonstraram que TGF-β, activinas e BMPs expressam receptores específicos a nível de RNA mensageiro em células do EPR.

Conclusões:

O presente estudo sugere que membros da superfamília de TGF-β podem exercer efeitos nas células de EPR D407 através de seus receptores específicos.

Palavras chave:
Receptor da superfamília TGF-β; Células do epitélio pigmentário da retina; Reação em cadeia da polimerase

Full text available only in PDF format.

REFERENCES

¹
Yamashita H, Hori S, Masuda K. Population and proportion of component cells in preretinal membranes. Jpn J Ophthalmol 1986;30:269-81.
²
Liversidge J, McKay D, Mullen G, Forrester JV. Retinal Pigment Epithelial Cells Modulate Lymphocyte Function at the Blood-Retina Barrier by Autoerine PGE2 and Membrane-Bound Mechanisms. Cell Immunol 1993;149:315-330.
³
Machemer R, Laqua H. Pigment epithelium proliferation i n retinal detachment (massive periretinal proliferation). Am J Ophthalmol 1975;80:1-23.
⁴
Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-beta. lmmunol Today 1989;10:258-61.
⁵
Leschey KH, Hachett SF, Singer JH, Campochiaro PA. Growth factor responsiviness of human retinal pigment epithelial cells. lnvest Ophthalmol Vis Sci 1990;31:839-46.
⁶
Sheu SJ, Sakamoto T, Osusky R, Wang HM , Ogden TE, Ryan SJ, Hinton DR, Gopalakrishna R. Transforming growth factor beta regulates human retinal pigment epithelial cell phagocytosis by influencing a protein C-dependent pathway. Graefe's Arch Clin Exp Ophthalmol 1994;232:695-701.
⁷
Murphy TL, Sakamoto T, Hinton DR, Spee C, Gundimeda U, Soriano D, Gopalakrishna R, Ryan SJ. Migration of retinal pigment epithelium cells in vitro is regulated by protein kinase C. Exp Eye Res 1995;60:683-95.
⁸
Gabrielian K, Osusky R, Sippy BD, Ryan SJ, Hinton DR. Effect of TGF-beta on Interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells Invest Ophthalmol Vis Sci 1994;35:4253-59.
⁹
Osusky R, Soriano D, Ye J, Ryan SJ. Cytokyne effect on fibronectin release by retinal pigment epithelial cells Cur Eye Res 1994;13:569-74.
¹⁰
Lutty GA, Merges C, Threlkeld AB, Crone S, McLeod DS. Heterogeneity in Localization of Isoforms of TGF-beta in Human Retina, Vitreous, and Choroid. Invest Ophthalmol Vis Sci 1993;34:477-87.
¹¹
Pfeffer BA, Flanders KC, Guérin CJ, Danielpour D, Anderson DH. Transforming growth factor beta 2 is the predominant isoform in the neural retina, retinal pigment epithelium-choroid and vitreous of the monkey eye. Exp Eye Res 1994;59:323-33.
¹²
Anderson DH, Guérin CJ, Hageman GS, Pfeffer BA, Flanders KC. Distribution of transforming growth factor beta isoforms in the mammalian retina. J Neurosci Res 1995;42:63-79.
¹³
Tanihara H, Yoshida M, Matsumoto M, Yoshimura N. Iddentification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1993;34:413-19.
¹⁴
Jaffe GJ, Harrison CE, Lui GM, Roberts WL, Goldsmith PC, Mesiano S, Jaffe RB. Activin expression by cultured pigment epithelial cells. Invest Ophthalmol Vis Sci 1994;35:2924-31.
¹⁵
Kvanta A. Expression and secretion of transforming growth factor-beta in transformed and nontransformed retinal pigment epithelial cells. Ophthalmic Res 1994;26:361-7.
¹⁶
Davis AA, Berstein PS, Bok D, Turner J, Nachtigal M, Hunt RC. A human retinal pigment epithelial cell line that retains epithelial characteristics after prolonged culture. Invest Ophthalmol Vis Sci 1995;36:955-64.
¹⁷
Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biolo 1988;106:761-71.
¹⁸
Game S M, Huelsen A, Patel V, Donnelly M, Yeudall W A, Stone A, Fusenig N E, Prime S S. Progressive abrogation of TGF-beta and EGF growth control is associated with tumour progression in ras-transfected human keratinocytes. Int J Cancer 1992;52:461-70.
¹⁹
Yoshimura N, Matsumoto M, Shimizu H, Mandai M, Hata Y, Ishibashi T. Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. Invest Ophthalmol Vis Sci 1995;36:1686-91.
²⁰
Matsumoto M, Yoshimura N, Honda Y. Increased production of transforming growth factor beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. Invest Ophthalmol Vis Sci 1994;34:4245-52.
²¹
Miyazono K, Dijke P.ten, Yamashita H, Heldin CH. Signal transduction via serine/threonine kinase receptors. Seminars in Cell Biology 1994;5:389-98.
²²
Miyazono K, Dijke P.ten, Ichiji H, Heldin CH. Receptors for transforming growth factor-beta. Advances in Immunol 1994;55:181-220.

Publication Dates

Publication in this collection
Apr 1998

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

[1] ¹
Yamashita H, Hori S, Masuda K. Population and proportion of component cells in preretinal membranes. Jpn J Ophthalmol 1986;30:269-81.

[2] ²
Liversidge J, McKay D, Mullen G, Forrester JV. Retinal Pigment Epithelial Cells Modulate Lymphocyte Function at the Blood-Retina Barrier by Autoerine PGE2 and Membrane-Bound Mechanisms. Cell Immunol 1993;149:315-330.

[3] ³
Machemer R, Laqua H. Pigment epithelium proliferation i n retinal detachment (massive periretinal proliferation). Am J Ophthalmol 1975;80:1-23.

[4] ⁴
Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-beta. lmmunol Today 1989;10:258-61.

[5] ⁵
Leschey KH, Hachett SF, Singer JH, Campochiaro PA. Growth factor responsiviness of human retinal pigment epithelial cells. lnvest Ophthalmol Vis Sci 1990;31:839-46.

[6] ⁶
Sheu SJ, Sakamoto T, Osusky R, Wang HM , Ogden TE, Ryan SJ, Hinton DR, Gopalakrishna R. Transforming growth factor beta regulates human retinal pigment epithelial cell phagocytosis by influencing a protein C-dependent pathway. Graefe's Arch Clin Exp Ophthalmol 1994;232:695-701.

[7] ⁷
Murphy TL, Sakamoto T, Hinton DR, Spee C, Gundimeda U, Soriano D, Gopalakrishna R, Ryan SJ. Migration of retinal pigment epithelium cells in vitro is regulated by protein kinase C. Exp Eye Res 1995;60:683-95.

[8] ⁸
Gabrielian K, Osusky R, Sippy BD, Ryan SJ, Hinton DR. Effect of TGF-beta on Interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells Invest Ophthalmol Vis Sci 1994;35:4253-59.

[9] ⁹
Osusky R, Soriano D, Ye J, Ryan SJ. Cytokyne effect on fibronectin release by retinal pigment epithelial cells Cur Eye Res 1994;13:569-74.

[10] ¹⁰
Lutty GA, Merges C, Threlkeld AB, Crone S, McLeod DS. Heterogeneity in Localization of Isoforms of TGF-beta in Human Retina, Vitreous, and Choroid. Invest Ophthalmol Vis Sci 1993;34:477-87.

[11] ¹¹
Pfeffer BA, Flanders KC, Guérin CJ, Danielpour D, Anderson DH. Transforming growth factor beta 2 is the predominant isoform in the neural retina, retinal pigment epithelium-choroid and vitreous of the monkey eye. Exp Eye Res 1994;59:323-33.

[12] ¹²
Anderson DH, Guérin CJ, Hageman GS, Pfeffer BA, Flanders KC. Distribution of transforming growth factor beta isoforms in the mammalian retina. J Neurosci Res 1995;42:63-79.

[13] ¹³
Tanihara H, Yoshida M, Matsumoto M, Yoshimura N. Iddentification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1993;34:413-19.

[14] ¹⁴
Jaffe GJ, Harrison CE, Lui GM, Roberts WL, Goldsmith PC, Mesiano S, Jaffe RB. Activin expression by cultured pigment epithelial cells. Invest Ophthalmol Vis Sci 1994;35:2924-31.

[15] ¹⁵
Kvanta A. Expression and secretion of transforming growth factor-beta in transformed and nontransformed retinal pigment epithelial cells. Ophthalmic Res 1994;26:361-7.

[16] ¹⁶
Davis AA, Berstein PS, Bok D, Turner J, Nachtigal M, Hunt RC. A human retinal pigment epithelial cell line that retains epithelial characteristics after prolonged culture. Invest Ophthalmol Vis Sci 1995;36:955-64.

[17] ¹⁷
Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biolo 1988;106:761-71.

[18] ¹⁸
Game S M, Huelsen A, Patel V, Donnelly M, Yeudall W A, Stone A, Fusenig N E, Prime S S. Progressive abrogation of TGF-beta and EGF growth control is associated with tumour progression in ras-transfected human keratinocytes. Int J Cancer 1992;52:461-70.

[19] ¹⁹
Yoshimura N, Matsumoto M, Shimizu H, Mandai M, Hata Y, Ishibashi T. Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. Invest Ophthalmol Vis Sci 1995;36:1686-91.

[20] ²⁰
Matsumoto M, Yoshimura N, Honda Y. Increased production of transforming growth factor beta 2 from cultured human retinal pigment epithelial cells by photocoagulation. Invest Ophthalmol Vis Sci 1994;34:4245-52.

[21] ²¹
Miyazono K, Dijke P.ten, Yamashita H, Heldin CH. Signal transduction via serine/threonine kinase receptors. Seminars in Cell Biology 1994;5:389-98.

[22] ²²
Miyazono K, Dijke P.ten, Ichiji H, Heldin CH. Receptors for transforming growth factor-beta. Advances in Immunol 1994;55:181-220.

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