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

doi:10.1016/j.bbrc.2013.11.066

Cited by 48 publications

(38 citation statements)

References 32 publications

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“…Both proteins are responsible for the early autophagosome formation. Previous studies have already shown that knock-out of ATG5 led to an inevitably reduced transfer of autophagy substrates into the lysosomes [16], [24]. Moreover, it has been previously described that ATG5 in complex with ATG12 is essential for the formation of autophagosomes [13], [25].…”

Section: Discussionmentioning

confidence: 96%

Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

et al. 2016

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The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of ATG5-ATG12, LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.

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Section: Discussionmentioning

confidence: 96%

Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

et al. 2016

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“…The underlying mechanism may involve alterations in cellular components and degradation of ECM components, including collagen and elastin fibers, in the dermis [44]. Tashiro et al demonstrated that UVB irradiation increased MMP expression and suppressed type I collagen synthesis [31]. Many studies have shown that exposure to UVB upregulates MMP expression, including MMP-1 (collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin), and MMP-9 (gelatinase B), which contributes to the degradation of type I collagen [45, 46].…”

Section: Discussionmentioning

confidence: 99%

“…The amount of soluble protein was divided by the cell number as a marker of cellular hypertrophy (protein/cell). Western blotting analysis of cellular proteins was performed according to a previously described method [31]. For the analysis, total cellular proteins were isolated using RIPA buffer (Sigma-Aldrich, St. Louis, MO, USA) 48 h after RAPA treatment.…”

Section: Methodsmentioning

confidence: 99%

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species

Qin

Ren

Jia

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm²), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. Methods: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated β-galactosidase (SA-β-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. Results: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-β-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. Conclusions: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study.

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“…Thinner and wrinkled skin-typical signs of normal aging-result from reduced collagen [7]. Protein glycation contributes to skin aging as it degrades existing collagen molecules by crosslinking [8].…”

Section: Introductionmentioning

confidence: 99%

Secondhand smoke exposure-induced nucleocytoplasmic shuttling of HMGB1 in a rat premature skin aging model

Chaichalotornkul¹,

Nararatwanchai²,

Narkpinit³

et al. 2015

Biochemical and Biophysical Research Communications

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Secondhand cigarette smoke exposure (SSE) has been linked to carcinogenic, oxidative, and inflammatory reactions. Herein, we investigated whether premature skin aging could be induced by SSE in a rat model, and assessed the cytoplasmic translocation of high mobility group box 1 (HMGB1) protein and collagen loss in skin tissues. Animals were divided into two groups: SSE and controls. Whole body SSE was carried out for 12 weeks. Dorsal skin tissue specimens were harvested for HMGB1 and Mallory's azan staining. Correlations between serum HMGB1 and collagen levels were determined. Rat skin exposed to secondhand smoke lost collagen bundles in the papillary dermis and collagen decreased significantly (p<0.05) compared with control rats. In epidermal keratinocytes, cytoplasmic HMGB1 staining was more diffuse and there were more HMGB1-positive cells after four weeks in SSE compared to control rats. A negative correlation between HMGB1 serum and collagen levels (r=-0.631, p=0.28) was also observed. Therefore, cytoplasmic HMGB1 expression in skin tissues might be associated with skin collagen loss upon the initiation of SSE. Additionally, long-term SSE might affect the appearance of the skin, or could accelerate the skin aging process.

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

Cited by 48 publications

References 32 publications

Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species

Secondhand smoke exposure-induced nucleocytoplasmic shuttling of HMGB1 in a rat premature skin aging model

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