Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes

Author:

Jang Hye-Yeon12,Kim Gi-Beum1,Kim Jeong-Mi1ORCID,Kang Sang Yull3,Youn Hyun-Jo3,Park Jinny4,Ro Su Yeon5,Chung Eun-Yong5,Park Kwang-Hyun67,Kim Jong-Suk1

Affiliation:

1. Department of Biochemistry and Molecular Biology, Institute for Medical Sciences, BK21FOUR 21st Century Medical Science Creative Human Resource Development Center, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea

2. Infectious Diseases Therapeutic Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea

3. Department of Surgery, Research Institute of Clinical Medicine, Jeonbuk National University Hospital, Biomedical Research Institute, Jeonbuk National University, Jeonju 54907, Republic of Korea

4. Department of Medical Oncology and Hematology, Ansan Hospital, Korea University College of Medicine, Ansan 15355, Republic of Korea

5. Department of Anesthesiology and Pain Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Republic of Korea

6. Department of Emergency Medical Rescue, Nambu University, Gwangju 62271, Republic of Korea

7. BioMedical Science Graduate Program (BMSGP), Department of Emergency Medicine, Chonnam National University, Hwasun 58128, Republic of Korea

Abstract

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs.

Funder

BK21FOUR 21st Century of Medical Science Creative Human Resource Development Center

Korean government

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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