Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells

Kazuhiro Kimura, Tomoko Orita, Youichiro Fujitsu, Yang Liu, Makiko Wakuta, Naoyuki Morishige, Katsuyoshi Suzuki, Koh Hei Sonoda

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose. Collagen contraction mediated by retinal pigment epithelial (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR). We examined the effects of sex hormones on this process. Methods. Mouse RPE cells were cultured in a type I collagen gel and exposed to 17β-estradiol, progesterone, or dehydro-epiandrosterone. Collagen contraction induced by transforming growth factor-β2 (TGF-β2) was determined by measurement of gel diameter. Expression of α-smooth muscle actin (α-SMA), as well as phosphorylation of Smad2 and myosin light chain (MLC), was examined by immunoblot analysis. Matrix metalloproteinase (MMP) release was evaluated by gelatin zymography. Fibronectin and interleukin-6 secretion was measured with immunoassays. Results. The female sex hormones 17β-estradiol and progesterone inhibited TGF-β2-induced collagen contraction mediated by RPE cells, whereas the male sex hormone dehydro-epiandrosterone had no such effect. The TGF-β2-induced release of MMP-2 and MMP-9 from RPE cells was also inhibited by 17β-estradiol and progesterone, and the MMP inhibitor GM6001 attenuated TGF-β2-induced collagen contraction. Expression of the mesenchymal markers α-SMA and fibronectin, interleukin-6 release, and Smad2 and MLC phosphorylation induced by TGF-β2 were all inhibited by 17β-estradiol and progesterone. Immunohistochemical analysis also detected nuclear immunoreactivity for estrogen and progesterone receptors in proliferative fibrocellular membranes of PVR patients. Conclusions. Female sex hormones inhibited TGF-β2-induced collagen contraction mediated by RPE cells. This action appeared to be mediated through inhibition both of MMP, α-SMA, and fibronectin expression as well as of Smad2 and MLC phosphorylation. Female sex hormones might thus prove effective for the treatment of PVR.

Original languageEnglish
Pages (from-to)2621-2630
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number4
DOIs
Publication statusPublished - Mar 7 2014
Externally publishedYes

Fingerprint

Retinal Pigments
Gonadal Steroid Hormones
Transforming Growth Factors
Collagen
Gels
Epithelial Cells
Proliferative Vitreoretinopathy
Myosin Light Chains
Progesterone
Estradiol
Fibronectins
Androsterone
Phosphorylation
Matrix Metalloproteinases
Interleukin-6
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Progesterone Receptors
Gelatin

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells. / Kimura, Kazuhiro; Orita, Tomoko; Fujitsu, Youichiro; Liu, Yang; Wakuta, Makiko; Morishige, Naoyuki; Suzuki, Katsuyoshi; Sonoda, Koh Hei.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 4, 07.03.2014, p. 2621-2630.

Research output: Contribution to journalArticle

Kimura, Kazuhiro ; Orita, Tomoko ; Fujitsu, Youichiro ; Liu, Yang ; Wakuta, Makiko ; Morishige, Naoyuki ; Suzuki, Katsuyoshi ; Sonoda, Koh Hei. / Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 4. pp. 2621-2630.
@article{feab34aa76d14ac3b6ef40536a5db94b,
title = "Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells",
abstract = "Purpose. Collagen contraction mediated by retinal pigment epithelial (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR). We examined the effects of sex hormones on this process. Methods. Mouse RPE cells were cultured in a type I collagen gel and exposed to 17β-estradiol, progesterone, or dehydro-epiandrosterone. Collagen contraction induced by transforming growth factor-β2 (TGF-β2) was determined by measurement of gel diameter. Expression of α-smooth muscle actin (α-SMA), as well as phosphorylation of Smad2 and myosin light chain (MLC), was examined by immunoblot analysis. Matrix metalloproteinase (MMP) release was evaluated by gelatin zymography. Fibronectin and interleukin-6 secretion was measured with immunoassays. Results. The female sex hormones 17β-estradiol and progesterone inhibited TGF-β2-induced collagen contraction mediated by RPE cells, whereas the male sex hormone dehydro-epiandrosterone had no such effect. The TGF-β2-induced release of MMP-2 and MMP-9 from RPE cells was also inhibited by 17β-estradiol and progesterone, and the MMP inhibitor GM6001 attenuated TGF-β2-induced collagen contraction. Expression of the mesenchymal markers α-SMA and fibronectin, interleukin-6 release, and Smad2 and MLC phosphorylation induced by TGF-β2 were all inhibited by 17β-estradiol and progesterone. Immunohistochemical analysis also detected nuclear immunoreactivity for estrogen and progesterone receptors in proliferative fibrocellular membranes of PVR patients. Conclusions. Female sex hormones inhibited TGF-β2-induced collagen contraction mediated by RPE cells. This action appeared to be mediated through inhibition both of MMP, α-SMA, and fibronectin expression as well as of Smad2 and MLC phosphorylation. Female sex hormones might thus prove effective for the treatment of PVR.",
author = "Kazuhiro Kimura and Tomoko Orita and Youichiro Fujitsu and Yang Liu and Makiko Wakuta and Naoyuki Morishige and Katsuyoshi Suzuki and Sonoda, {Koh Hei}",
year = "2014",
month = "3",
day = "7",
doi = "10.1167/iovs.13-13501",
language = "English",
volume = "55",
pages = "2621--2630",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "4",

}

TY - JOUR

T1 - Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells

AU - Kimura, Kazuhiro

AU - Orita, Tomoko

AU - Fujitsu, Youichiro

AU - Liu, Yang

AU - Wakuta, Makiko

AU - Morishige, Naoyuki

AU - Suzuki, Katsuyoshi

AU - Sonoda, Koh Hei

PY - 2014/3/7

Y1 - 2014/3/7

N2 - Purpose. Collagen contraction mediated by retinal pigment epithelial (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR). We examined the effects of sex hormones on this process. Methods. Mouse RPE cells were cultured in a type I collagen gel and exposed to 17β-estradiol, progesterone, or dehydro-epiandrosterone. Collagen contraction induced by transforming growth factor-β2 (TGF-β2) was determined by measurement of gel diameter. Expression of α-smooth muscle actin (α-SMA), as well as phosphorylation of Smad2 and myosin light chain (MLC), was examined by immunoblot analysis. Matrix metalloproteinase (MMP) release was evaluated by gelatin zymography. Fibronectin and interleukin-6 secretion was measured with immunoassays. Results. The female sex hormones 17β-estradiol and progesterone inhibited TGF-β2-induced collagen contraction mediated by RPE cells, whereas the male sex hormone dehydro-epiandrosterone had no such effect. The TGF-β2-induced release of MMP-2 and MMP-9 from RPE cells was also inhibited by 17β-estradiol and progesterone, and the MMP inhibitor GM6001 attenuated TGF-β2-induced collagen contraction. Expression of the mesenchymal markers α-SMA and fibronectin, interleukin-6 release, and Smad2 and MLC phosphorylation induced by TGF-β2 were all inhibited by 17β-estradiol and progesterone. Immunohistochemical analysis also detected nuclear immunoreactivity for estrogen and progesterone receptors in proliferative fibrocellular membranes of PVR patients. Conclusions. Female sex hormones inhibited TGF-β2-induced collagen contraction mediated by RPE cells. This action appeared to be mediated through inhibition both of MMP, α-SMA, and fibronectin expression as well as of Smad2 and MLC phosphorylation. Female sex hormones might thus prove effective for the treatment of PVR.

AB - Purpose. Collagen contraction mediated by retinal pigment epithelial (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR). We examined the effects of sex hormones on this process. Methods. Mouse RPE cells were cultured in a type I collagen gel and exposed to 17β-estradiol, progesterone, or dehydro-epiandrosterone. Collagen contraction induced by transforming growth factor-β2 (TGF-β2) was determined by measurement of gel diameter. Expression of α-smooth muscle actin (α-SMA), as well as phosphorylation of Smad2 and myosin light chain (MLC), was examined by immunoblot analysis. Matrix metalloproteinase (MMP) release was evaluated by gelatin zymography. Fibronectin and interleukin-6 secretion was measured with immunoassays. Results. The female sex hormones 17β-estradiol and progesterone inhibited TGF-β2-induced collagen contraction mediated by RPE cells, whereas the male sex hormone dehydro-epiandrosterone had no such effect. The TGF-β2-induced release of MMP-2 and MMP-9 from RPE cells was also inhibited by 17β-estradiol and progesterone, and the MMP inhibitor GM6001 attenuated TGF-β2-induced collagen contraction. Expression of the mesenchymal markers α-SMA and fibronectin, interleukin-6 release, and Smad2 and MLC phosphorylation induced by TGF-β2 were all inhibited by 17β-estradiol and progesterone. Immunohistochemical analysis also detected nuclear immunoreactivity for estrogen and progesterone receptors in proliferative fibrocellular membranes of PVR patients. Conclusions. Female sex hormones inhibited TGF-β2-induced collagen contraction mediated by RPE cells. This action appeared to be mediated through inhibition both of MMP, α-SMA, and fibronectin expression as well as of Smad2 and MLC phosphorylation. Female sex hormones might thus prove effective for the treatment of PVR.

UR - http://www.scopus.com/inward/record.url?scp=84899652463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899652463&partnerID=8YFLogxK

U2 - 10.1167/iovs.13-13501

DO - 10.1167/iovs.13-13501

M3 - Article

C2 - 24609629

AN - SCOPUS:84899652463

VL - 55

SP - 2621

EP - 2630

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 4

ER -