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

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.

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Antiphotoaging Effect of 3,5-Dicaffeoyl-epi-quinic Acid against UVA-Induced Skin Damage by Protecting Human Dermal Fibroblasts In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms21207756 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7756

Author(s):

Jung Hwan Oh ◽

Fatih Karadeniz ◽

Chang-Suk Kong ◽

Youngwan Seo

Keyword(s):

Molecular Mechanisms ◽

Type I Collagen ◽

Nuclear Translocation ◽

Quinic Acid ◽

Dermal Fibroblasts ◽

Type I ◽

Human Dermal Fibroblasts ◽

Skin Damage ◽

Chronological Aging

Cutaneous aging is divided into intrinsic and exogenous aging correspondingly contributing to the complex biological phenomenon in skin. Intrinsic aging is also termed chronological aging, which is the accumulation of inevitable changes over time and is largely genetically determined. Superimposed on this intrinsic process, exogenous aging is associated with environmental exposure, mainly to ultraviolet (UV) radiation and more commonly termed as photoaging. UV-induced skin aging induces increased expression of matrix metalloproteinases (MMPs) which in turn causes the collagen degradation. Therefore, MMP inhibitors of natural origin are regarded as a primary approach to prevent or treat photoaging. This study investigated the effects of 3,5-dicaffeoyl-epi-quinic acid (DEQA) on photoaging and elucidated its molecular mechanisms in UVA-irradiated human dermal fibroblasts (HDFs). The results show that treatment with DEQA decreases MMP-1 production and increases type I collagen production in UVA-damaged HDFs. In addition, treatment of UVA-irradiated HDFs with DEQA downregulates MMP-1, MMP-3 and MMP-9 expression via blocking MAPK-cascade-regulated AP-1 transcriptional activity in UVA-irradiated HDFs. Furthermore, DEQA relieves the UVA-mediated suppression of type I procollagen and collagen expression through stimulating TGF-β/Smad signaling, leading to activation of the Smad 2/3 and Smad 4 nuclear translocation. These results suggest that DEQA could be a potential cosmetic agent for prevention and treatment of skin photoaging.

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Dermal Olfactory Receptor OR51B5 Is Essential for Survival and Collagen Synthesis in Human Dermal Fibroblast (Hs68 Cells)

International Journal of Molecular Sciences ◽

10.3390/ijms22179273 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9273

Author(s):

Bomin Son ◽

Wesuk Kang ◽

Soyoon Park ◽

Dabin Choi ◽

Taesun Park

Keyword(s):

Cell Survival ◽

Collagen Synthesis ◽

Dermal Fibroblast ◽

Olfactory Receptors ◽

Camp Response Element Binding ◽

Human Dermal Fibroblast ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Nasal Tissue ◽

Extracellular Matrix Components

Skin dermis comprises extracellular matrix components, mainly collagen fibers. A decrease in collagen synthesis caused by several factors, including ultraviolet (UV) irradiation and stress, eventually causes extrinsic skin aging. Olfactory receptors (ORs) were initially considered to be specifically expressed in nasal tissue, but several ORs have been reported to be present in other tissues, and their biological roles have recently received increasing attention. In this study, we aimed to characterize the role of ORs in cell survival and collagen synthesis in dermal fibroblasts. We confirmed that UVB irradiation and dexamethasone exposure significantly decreased cell survival and collagen synthesis in Hs68 dermal fibroblasts. Moreover, we demonstrated that the mRNA expression of 10 ORs detectable in Hs68 cells was significantly downregulated in aged conditions compared with that in normal conditions. Thereafter, by individual knockdown of the 10 candidate ORs, we identified that only OR51B5 knockdown leads to a reduction of cell survival and collagen synthesis. OR51B5 knockdown decreased cAMP levels and dampened the downstream protein kinase A/cAMP-response element binding protein pathway, downregulating the survival- and collagen synthesis-related genes in the dermal fibroblasts. Therefore, OR51B5 may be an interesting candidate that plays a role in cell survival and collagen synthesis.

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The anti-skin-aging effect of oral administration of gelatin from the swim bladder of Amur sturgeon (Acipenser schrenckii)

Food & Function ◽

10.1039/c9fo00661c ◽

2019 ◽

Vol 10 (7) ◽

pp. 3890-3897 ◽

Cited By ~ 4

Author(s):

Lin Wang ◽

Xiaoxiao Wang ◽

Fan Bai ◽

Yong Fang ◽

Jinlin Wang ◽

...

Keyword(s):

Oral Administration ◽

Type I Collagen ◽

Aging Effect ◽

Skin Aging ◽

Hot Water ◽

Type I ◽

Swim Bladder ◽

Amur Sturgeon

Gelatin was extracted from the swim bladder of Amur sturgeon with hot water at 50 °C with acceptable yield (76.54%) and it showed and type I collagen features.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21228693 ◽

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.

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Evaluation of the efficacy of ethanol leaf extract of Helichrysum petiolare Hilliard and B.L. Burtt against skin aging

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i12.22 ◽

2021 ◽

Vol 19 (12) ◽

pp. 2631-2638

Author(s):

Idowu Jonas Sagbo ◽

Wilfred Otang-Mbeng

Keyword(s):

Leaf Extract ◽

Dermal Fibroblast ◽

Stress Protein ◽

Inhibitory Effect ◽

Human Dermal Fibroblast ◽

Skin Aging ◽

Protein Glycation ◽

No Production ◽

Dependent Manner ◽

Concentration Dependent Manner

Purpose: To determine the efficacy of Helichrysum petiolare ethanol leaf extract against skin aging.Methods: The cytotoxic potential of the plant extract towards human dermal fibroblast (MRHF) cells was determined by Hoechst 33342/Propidium iodide (PI) staining. Effect of H. petiolare extract on reactive oxygen species (ROS) levels in MRHF cells and NO (nitric oxide) production in RAW 246.7 cells activated by LPS (lipopolysaccharides) was investigated. The inhibitory effect of the extract againstcollagenase, elastase, tyrosinase and protein glycation was also evaluated.Results: The extract did not display cytotoxicity towards MRHF cells at the tested concentrations when compared to the trend seen with the untreated control (p < 0.05). The extract caused a significant decrease (p < 0.05) in ROS levels in MRHF cells in a concentration-dependent manner and also demonstrated a reduction in NO production in RAW cells with no toxicity. Furthermore, the extract produced a weak inhibition of collagenase, elastase and tyrosinase activities when compared to the corresponding positive controls, but effectively inhibited protein glycation at the tested concentrations.Conclusion: The findings suggest that the ethanol leaf extract from H. petiolare has the potential to mitigate skin aging and therefore needs to be further investigated for possible clinical applications. Keywords: Cytotoxicity, Efficacy, Helichrysum petiolare, MRHF cells, Oxidative stress, Protein glycation; skin aging

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Modulation by 17,20S(OH)2pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms23010367 ◽

2021 ◽

Vol 23 (1) ◽

pp. 367

Author(s):

Monica L. Brown Lobbins ◽

Andrzej T. Slominski ◽

Karen A. Hasty ◽

Sicheng Zhang ◽

Duane D. Miller ◽

...

Keyword(s):

Systemic Sclerosis ◽

Type I Collagen ◽

Dermal Fibroblast ◽

Positive Control ◽

Dermal Fibroblasts ◽

Normal Donor ◽

Type I ◽

Collagen Production ◽

Healthy Donors ◽

Tgf Β1

We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.

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

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.633331 ◽

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.

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Evaluation of Gallic Acid-Coated Gold Nanoparticles as an Anti-Aging Ingredient

Pharmaceuticals ◽

10.3390/ph14111071 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1071

Author(s):

Yun-Zhen Wu ◽

Yen-Yu Tsai ◽

Long-Sen Chang ◽

Ying-Jung Chen

Keyword(s):

Gold Nanoparticles ◽

Gallic Acid ◽

High Glucose ◽

Type I Collagen ◽

Dermal Fibroblast ◽

Skin Aging ◽

Hydrodynamic Diameter ◽

Type I ◽

Matrix Metalloproteinase 1 ◽

Transmission Electron

Hyperglycemic environment-induced oxidative stress-mediated matrix metalloproteinase-1 (MMP-1) plays a crucial role in the degradation of the extracellular matrix (ECM), which might contribute to premature skin aging. Synthesized, environmentally friendly gallic acid-coated gold nanoparticles (GA–AuNPs) have been evaluated as an anti-aging antioxidant. Their microstructure was characterized by transmission electron microscopy (TEM), which showed that GA–AuNPs are spherical when prepared at pH 11. Dynamic light scattering (DLS) analysis revealed that the average hydrodynamic diameter of a GA–AuNP is approximately 40 nm and with a zeta potential of −49.63 ± 2.11 mV. Additionally, the present data showed that GA–AuNPs have a superior ability to inhibit high glucose-mediated MMP-1-elicited type I collagen degradation in dermal fibroblast cells. Collectively, our data indicated that high-glucose-mediated ROS production was reduced upon cell treatment with GA–AuNPs, which blocked p38 MAPK/ERK-mediated c-Jun, c-Fos, ATF-2 phosphorylation, and the phosphorylation of NFκB, leading to the down-regulation of MMP-1 mRNA and protein expression in high glucose-treated cells. Our findings suggest that GA-AuNPs have a superior ability to inhibit high-glucose-mediated MMP-1-elicited ECM degradation, which highlights its potential as an anti-aging ingredient.

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A bioactive collagen-β tricalcium phosphate scaffold for tissue engineering

Open Life Sciences ◽

10.2478/s11535-006-0005-7 ◽

2006 ◽

Vol 1 (1) ◽

pp. 61-72 ◽

Cited By ~ 7

Author(s):

Elena Oprita ◽

Lucia Moldovan ◽

Oana Craciunescu ◽

Wanda Buzgariu ◽

Christu Tardei ◽

...

Keyword(s):

Tricalcium Phosphate ◽

Type I Collagen ◽

Dermal Fibroblast ◽

Human Dermal Fibroblast ◽

Type I ◽

X Ray Diffraction ◽

Bioactive Materials ◽

In Vitro Biocompatibility ◽

And Migration

AbstractCollagen-phosphate composites (COL/β-TCP) are novel materials that have the potential to be used as bone analogues. The aim of our study was to develop a porous bioactive material composed of type I collagen, the main bone protein and tricalcium phosphate, the mineral phase of natural bone, and investigate their in vitro biocompatibility in a human dermal fibroblast culture system. In order to obtain the bioactive materials, type I collagen was isolated from bovine tendon and characterized by physicochemical methods. β-TCP was obtained from calcium carbonate by thermal decomposition at 900 °C temperature. The powder was examined with X-ray diffraction. Two variants of COL/β-TCP scaffolds (P1 and P2) were prepared and examined by scanning electron microscopy. Our results revealed a microporous structure with small white aggregates of β-TCP, non-homogenous scattered in the collagen framework without any preferential orientation. The biocompatibility of the obtained scaffolds was tested by biochemical and histological methods on human fibroblast cultures. Both materials acted as good subtrates for human dermal fibroblast proliferation and migration.

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Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis

Scientific Reports ◽

10.1038/s41598-020-74179-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Pernille Juhl ◽

Sandie Bondesen ◽

Clare Louise Hawkins ◽

Morten Asser Karsdal ◽

Anne-Christine Bay-Jensen ◽

...

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Type I Collagen ◽

Skin Diseases ◽

Dermal Fibroblast ◽

Dermal Fibroblasts ◽

Type I ◽

Healthy Human ◽

Clinical Model ◽

Collagen Formation

Abstract Different stimulants might induce different extracellular matrix profiles. It is essential to gain an understanding and quantification of these changes to allow for focused anti-fibrotic drug development. This study investigated the expression of extracellular matrix by dermal fibroblast mimicking fibrotic skin diseases as SSc using clinically validated biomarkers. Primary healthy human dermal fibroblasts were grown in media containing FICOLL. The cells were stimulated with PDGF-AB, TGF-β1, or IL-6. Anti-fibrotic compounds (iALK-5, Nintedanib) were added together with growth factors. Biomarkers of collagen formation and degradation together with fibronectin were evaluated by ELISAs in the collected supernatant. Immunohistochemical staining was performed to visualize fibroblasts and proteins, while selected gene expression levels were examined through qPCR. TGF-β and PDGF, and to a lesser extent IL-6, increased the metabolic activity of the fibroblasts. TGF-β primarily increased type I collagen and fibronectin protein and gene expression together with αSMA. PDGF stimulation resulted in increased type III and VI collagen formation and gene expression. IL-6 decreased fibronectin levels. iALK5 could inhibit TGF-β induced fibrosis while nintedanib could halt fibrosis induced by TGF-β or PDGF. Tocilizumab could not inhibit fibrosis induced in this model. The extent and nature of fibrosis are dependent on the stimulant. The model has potential as a pre-clinical model as the fibroblasts fibrotic phenotype could be reversed by an ALK5 inhibitor and Nintedanib.

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