scholarly journals Rapamycin Protects Skin Fibroblasts From UVA-Induced Photoaging by Inhibition of p53 and Phosphorylated HSP27

2021 ◽  
Vol 9 ◽  
Author(s):  
Gen-Long Bai ◽  
Ping Wang ◽  
Xin Huang ◽  
Zi-Yue Wang ◽  
Di Cao ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Aging Effects ◽  
Smad Signaling Pathway ◽  
Skin Photoaging ◽  
Dermal Collagen ◽  
Induced Apoptosis

Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.

scholarly journals Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects

2020 ◽  
Vol 21 (22) ◽  
pp. 8439
Author(s):  
Kyung-Eun Lee ◽  
Sugyeong Jeong ◽  
Seok Kyun Yun ◽  
Seoyeon Kyung ◽  
Abadie Sophie ◽  
...  
Keyword(s):  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Biologically Active ◽  
Type I ◽  
Aging Effects ◽  
Type I Procollagen ◽  
Reproductive Axis ◽  
Stress Related Genes ◽  
Active Fragments ◽  
Aging Models

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.

scholarly journals Anti-Aging Effects of Gyrophoric Acid on UVA-Irradiated Normal Human Dermal Fibroblasts

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2091954
Author(s):  
Joong Hyun Shim
Keyword(s):  
Mrna Expression ◽  
Type I Collagen ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Human Dermal Fibroblasts ◽  
Aging Effects ◽  
Expression Levels ◽  
Normal Human ◽  
Normal Human Dermal Fibroblasts ◽  
Gyrophoric Acid

This research was conducted to identify the anti-aging effects of gyrophoric acid on the skin, using normal human dermal fibroblasts. The anti-aging effects of gyrophoric acid on dermal fibroblasts were demonstrated through cell viability, verification of collagen, type I, alpha 1 (COL1A1)/COL3A1/matrix metalloproteinases 1 (MMP1) messenger ribonucleic acid (mRNA) expression levels with quantitative real-time reverse-transcription polymerase chain reaction, and protein estimation using type I collagen/MMP1-enzyme-linked immunosorbent assay. Further, the effects of gyrophoric acid on superoxide dismutases (SODs)/catalase were investigated by assessing their mRNA expression. In ultraviolet A (UVA)-treated dermal fibroblasts, gyrophoric acid was observed to increase mRNA levels of COL1A1/COL3A1/SOD2 genes and type I collagen protein levels, consistent with its anti-aging role. Furthermore, gyrophoric acid treatment decreased both MMP1 mRNA and protein expression levels. Therefore, the results of this study demonstrate that gyrophoric acid can be considered as an important natural compound with potent anti-aging effects on the skin. Based on the findings of this study, further research about the mechanism of action of gyrophoric acid should be pursued so as to develop novel anti-aging strategies not only in the field of cosmetics but also for healthcare.

scholarly journals Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

2020 ◽  
Vol 21 (22) ◽  
pp. 8693
Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Mrna Level ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Cell Physiology ◽  
Type I ◽  
Tenascin C ◽  
Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

scholarly journals Solid-State Fermentation With Aspergillus cristatus Enhances the Protopanaxadiol- and Protopanaxatriol-Associated Skin Anti-aging Activity of Panax notoginseng

2021 ◽  
Vol 12 ◽  
Author(s):  
Sunmin Lee ◽  
Chagam Koteswara Reddy ◽  
Jeoung Jin Ryu ◽  
Seoyeon Kyung ◽  
Yonghwan Lim ◽  
...  
Keyword(s):  
Solid State ◽  
Solid State Fermentation ◽  
Type I Collagen ◽  
Panax Notoginseng ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Aging Effects ◽  
Extracellular Matrix Components ◽  
Fibrillin 1 ◽  
Aspergillus Cristatus

A metabolomics approach was used to profile metabolites of Panax notoginseng fermented with Aspergillus cristatus in two ways, liquid-state fermentation (LF-P) and solid-state fermentation (SSF-P) and examine metabolite markers representing antioxidant activity and skin anti-aging. Protopanaxadiol (PPD) and protopanaxatriol (PPT) contents were higher in SSF-P than in LF-P and showed a multiplicative increase over the fermentation period of four days. PPD and PPT levels also correlated with antioxidant and anti-aging effects in skin, based on the mRNA expression of dermal extracellular matrix components. In the bioactivity validation assays, PPD and PPT significantly improved the expression of type-I collagen, fibrillin-1, and elastin in human dermal fibroblasts from both young and old subjects; these were comparable with the effects of the SSF-P extracts. Overall, our results suggest that changes in the metabolites of P. notoginseng fermented with A. cristatus enhance the quality and availability of bioactive compounds associated with skin anti-aging.

scholarly journals Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

2020 ◽  
Author(s):  
Young Eun Choi ◽  
Min Ji Song ◽  
Mari Hara ◽  
Kyoko Imanaka-Yoshida ◽  
Dong Hun Lee ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Mrna Level ◽  
Collagen Matrix ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Cell Physiology ◽  
Type I ◽  
Tenascin C ◽  
Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

scholarly journals The Role of microRNAs in Organismal and Skin Aging

2020 ◽  
Vol 21 (15) ◽  
pp. 5281
Author(s):  
Marta Gerasymchuk ◽  
Viktoriia Cherkasova ◽  
Olga Kovalchuk ◽  
Igor Kovalchuk
Keyword(s):  
Replicative Senescence ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Telomere Maintenance ◽  
Sirtuin 1 ◽  
Aging Effects ◽  
Inhibition Of Proliferation ◽  
Biomarkers Of Aging ◽  
Age Related

The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained.

scholarly journals The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Effects and Inflammatory Cytokines by 1α, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts

Cosmetics ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 46 ◽  
Author(s):  
Neena Philips ◽  
Xinxing Ding ◽  
Pranathi Kandalai ◽  
Ilonka Marte ◽  
Hunter Krawczyk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Oxidative Damage ◽  
Inflammatory Cytokines ◽  
Type I Collagen ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Stress Effects ◽  
Shock Proteins

Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation, are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1α, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. With regard to anti-inflammation, vitamin D inhibited expression of Il-1 and IL-8 in UVA-radiated fibroblasts, and stimulated HSP-70 in UVA-radiated and UVB-radiated fibroblasts. Overall, vitamin D is predominantly beneficial in preventing UVA-radiation induced photoaging through the differential regulation of the ECM, HSPs, and inflammatory cytokines, and protective effects on the cellular biomolecules. It is also beneficial in preventing UVB-radiation associated photoaging through the stimulation of cell viability and HSP-70, and the inhibition of cellular oxidative damage, and in preventing intrinsic aging through the stimulation of type I collagen and inhibition of cellular oxidative damage.

scholarly journals Acetylated Resveratrol and Oxyresveratrol Suppress UVB-Induced MMP-1 Expression in Human Dermal Fibroblasts

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1252
Author(s):  
Jae-Eun Lee ◽  
Jijeong Oh ◽  
Daeun Song ◽  
Mijeong Lee ◽  
Dongyup Hahn ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Dermal Fibroblast ◽  
Aging Effect ◽  
Inhibitory Effect ◽  
Human Dermal Fibroblast ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Hdf Cells

Resveratrol (RES) and oxyresveratrol (OXYRES) are considered and utilized as active ingredients of anti-aging skin cosmetics. However, these compounds are susceptible to oxidative discoloration and unpleasant odor in solutions, limiting their use in cosmetics. Accordingly, RES and OXYRES were chemically modified to acetylated derivatives with enhanced stability, and their anti-aging effect on the skin and detailed molecular mechanism of their acetylated derivatives were investigated. Acetylated RES and OXYRES lost their acetyl group and exerted an inhibitory effect on H2O2-induced ROS levels in human dermal fibroblast (HDF) cells. In addition, RES, OXYRES, and their acetylated derivatives suppressed UVB-induced matrix metalloproteinase (MMP)-1 expression via inhibition of mitogen-activated protein kinases (MAPKs) and Akt/mTOR signaling pathways. Furthermore, RES, OXYRES, and their acetylated derivatives suppressed type I collagen in TPA-treated HDF cells. Collectively, these results suggest the beneficial effects and underlying molecular mechanisms of RES, OXYRES, and their acetylated derivatives for anti- skin aging applications.

scholarly journals The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cell Metabolism ◽  
Breast Tumors ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Desmoplastic Reaction ◽  
The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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