FBN2
Fibrillin-2 precursor [Contains: Fibrillin-2 C-terminal peptide]
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Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, [i]Saccharomyces cerevisiae[/i] and [i]Rhodiola rosea[/i] root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of [i]Narcissus tazetta[/i] bulb extract and [i]Schisandra chinensis[/i] fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.
MeSH Terms
- Antioxidants
- Epigenesis, Genetic
- Gene Expression Regulation
- Humans
- MicroRNAs
- Narcissus
- Oxidative Stress
- Plant Extracts
- Plants, Medicinal
- Rhodiola
- Schisandra
- Skin
- Skin Aging
- Ultraviolet Rays
Keywords
- botanicals
- gene expression
- microRNA
- oxidative stress
- periorbital skin aging
- skin equivalents
The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low [i]versus[/i] high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism ([i]e.g.[/i] AACS, ACOX1, ACLY) and red-ox pathways ([i]e.g.[/i] CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response ([i]e.g.[/i] IGTB2, IFIT3, LGALS1) and rennin angiotensin system ([i]e.g.[/i] ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle ([i]e.g.[/i] OTC, ARG1, CPS1), and amino acid biosynthesis ([i]e.g.[/i] GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle ([i]e.g.[/i] ARG1, CPS1), immune response/complement activation ([i]e.g.[/i] C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling ([i]e.g.[/i] EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis ([i]e.g.[/i] YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.
MeSH Terms
- Adipose Tissue
- Aging
- Animals
- Diet, High-Fat
- Epididymis
- Gene Regulatory Networks
- Immunoblotting
- Male
- Mass Spectrometry
- Metabolic Networks and Pathways
- Mice, Inbred C57BL
- Proteome
- Proteomics
- Reproducibility of Results
- Sample Size