A Zingerone Analog, Acetyl Zingerone, Bolsters Matrisome Synthesis, Inhibits Matrix Metallopeptidases, and Represses IL-17A Target Gene Expression
| Autor: | Ratan K. Chaudhuri, William R. Swindell, Krzysztof Bojanowski |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Zingerone MMP3 Cellular differentiation Dermatology Biochemistry Extracellular matrix Tissue Culture Techniques 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Matrix Metalloproteinase 12 Gene expression medicine Humans Extracellular matrix disassembly Fibroblast Molecular Biology Oligonucleotide Array Sequence Analysis Gene Expression Profiling Guaiacol Interleukin-17 Cell Differentiation Cell Biology Cell biology Extracellular Matrix Skin Aging Gene expression profiling 030104 developmental biology medicine.anatomical_structure chemistry Gene Expression Regulation 030220 oncology & carcinogenesis Matrix Metalloproteinase 3 Epidermis |
| Zdroj: | The Journal of investigative dermatology. 140(3) |
| ISSN: | 1523-1747 |
| Popis: | Zingerone (Z) is a phenolic alkanone derived from natural sources with anti-inflammatory and antioxidant effects. Acetyl zingerone (AZ) is a recently designed molecule that shares structural features with Z but is expected to have improved stability and antioxidant function. This study utilized microarrays to compare the effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1 and MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3 and CTSV) and reactive oxygen species metabolism (PMAIP1 and ARG2). Although Z and AZ each inhibited in vitro matrix metallopeptidase (MMP)-1, MMP-3, and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens (COL11A2), proteoglycans (VCAN), and extracellular matrix glycoproteins (SPARC). Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation. These effects were AZ-specific and not replicated by Z. These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. Our findings provide a rationale for clinical studies to understand the benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases. |
| Databáze: | OpenAIRE |
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