Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

Kanae Tashiro, Mayumi Shishido, Keiko Fujimoto, Yuko Hirota, Kazuyuki Yo, Takamasa Gomi, Yoshitaka Tanaka

研究成果: ジャーナルへの寄稿記事

19 引用 (Scopus)

抄録

Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for autophagosome formation-was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

元の言語英語
ページ(範囲)167-172
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
443
発行部数1
DOI
出版物ステータス出版済み - 1 3 2014

Fingerprint

Autophagy
Fibroblasts
Extracellular Matrix
Skin
Aging of materials
Membranes
Lipofuscin
Elastin
Hyaluronic Acid
Skin Aging
Collagen Type I
Protease Inhibitors
Deterioration
Essential Genes
Microscopic examination
Collagen
Transmission Electron Microscopy
Fluorescence Microscopy
Genes
Tissue

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components. / Tashiro, Kanae; Shishido, Mayumi; Fujimoto, Keiko; Hirota, Yuko; Yo, Kazuyuki; Gomi, Takamasa; Tanaka, Yoshitaka.

:: Biochemical and Biophysical Research Communications, 巻 443, 番号 1, 03.01.2014, p. 167-172.

研究成果: ジャーナルへの寄稿記事

@article{1280257ab95e42e3a50bd426fe76e61d,
title = "Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components",
abstract = "Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for autophagosome formation-was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.",
author = "Kanae Tashiro and Mayumi Shishido and Keiko Fujimoto and Yuko Hirota and Kazuyuki Yo and Takamasa Gomi and Yoshitaka Tanaka",
year = "2014",
month = "1",
day = "3",
doi = "10.1016/j.bbrc.2013.11.066",
language = "English",
volume = "443",
pages = "167--172",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

AU - Tashiro, Kanae

AU - Shishido, Mayumi

AU - Fujimoto, Keiko

AU - Hirota, Yuko

AU - Yo, Kazuyuki

AU - Gomi, Takamasa

AU - Tanaka, Yoshitaka

PY - 2014/1/3

Y1 - 2014/1/3

N2 - Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for autophagosome formation-was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

AB - Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5-genes essential for autophagosome formation-was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

UR - http://www.scopus.com/inward/record.url?scp=84890857914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890857914&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2013.11.066

DO - 10.1016/j.bbrc.2013.11.066

M3 - Article

VL - 443

SP - 167

EP - 172

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -