Regulation Effect of 2',4',7-Trihydroxyisoflavone on the Expression of Matrix Metalloproteinase-1, 2 in Ultraviolet-B Irradiated Primary Cultured Old Aged Human Skin Fibroblasts

Abstract

Long term and repeated exposure of UV light on the skin often induces chronic skin diseases such as skin cancer as well as photoaging, and the mechanisms of these skin damages are closely associated with up-regulation of matrix metalloproteinase's (MMPs) activities. We investigated the effect of 2,4,7-trihydroxyisoflavone purified from the whole plants of Viola hondoensis W. BECKER et H BOISSIEU (Violaceae) on the expression of MMPs in UV-B irradiated old aged human skin fibroblasts. 2,4,7-trihydroxyisoflavone markedly reduced UV-induced MMP-1 expression, but not MMP-2, at the both mRNA and protein levels in a dose-dependent manner. Our report is the first description for the ability of 2,4,7-trihydroxyisoflavone to regulate MMP-1 expression from ultraviolet-B irradiated primary cultured old aged human skin fibroblasts.Key words Viola hondoensis; 2Ј,4Ј,7-trihydroxyisoflavone; matrix metalloproteinase (MMP)-1; MMP-2; aged human skin fibroblastThe skin aging process can be divided into intrinsic aging and photoaging. Damage to human skin due to repeated exposure to ultraviolet (UV) radiation (photoaging) and damage occurring as a result of the passage of time (intrinsic aging) are considered to be distinct entities rather than similar skin aging processes. Photoaging of skin is caused by genetically determined or intrinsic processes superimposed upon the degenerative changes due to solar radiation. 1) Alterations and deficiencies of collagen, the major structural component of skin, have been suggested to be a cause of the skin wrinkling observed in photoaged and naturally aged skin. 2,3)The dermis contains predominantly type I and type III collagen, elastin, proteoglycans, and fibronectin. Since collagen fibrils and elastin are responsible for the strength and resiliency of skin, their disarrangement during photoaging causes the skin to appear aged. Recently, it was suggested that excessive matrix degradation by UV-induced MMP-1 secreted by various cells, including, keratinocytes, fibroblasts, and inflammatory cells, contributes substantially to the connective tissue damage that occurs during photoaging. [4][5][6] The expression of MMPs proteins in the dermis of sunexposed and sun-protected skin of elderly subjects is known to differ. 5) Photodamaged skin of the elderly shows higher MMP-1 protein expression, than the intrinsically aged skin in the same individual.5) Thus, this resulting higher expression of MMP-1 in photoaged skin may cause severe collagen deficiency and wrinkling. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteinases that play pivotal roles in the dynamic remodeling of extracellular matrix. Based on substrate preference and structural homology, MMPs are sub-classified into functional groups: collagenases, gelatinases, stromelysins, matrilysins, membrane typeMMPs (MT-MMPs) and other non-classified MMPs. 7) MMPs are frequently overexpressed by the various extracellular stimuli including growth factors, cytokines, tumor promoters, and UV, and this increase in MMP-related ac...

A Glycosidic Spinasterol from Koreana stewartia Promotes Procollagen Production and Inhibits Matrix Metalloproteinase-1 Expression in UVB-Irradiated Human Dermal Fibroblasts

“…These results correlated well with a previous report that UV irradiation of cultured human skin fibroblasts induced upregulation of MMP-1, but had no effect on MMP-2. 31) In conclusion, the present study has shown that spinasterol-Glc isolated from Stewartia koreana promotes production of collagen in UV-irradiated fibroblast cells via stimulation of procollagen synthesis and via inhibition of MMP-1 expression. The underlying mechanisms by which spinasterol-Glc stimulates production of collagen and also inhibits MMP-1 expression in UV-irradiated fibroblast cells need to be elucidated.…”

“…It has been reported that many plant extracts stimulate collagen production and inhibit matrix metalloproteinases during photoaging. 13,16) Most plant-derived compounds promote collagen production in human skin fibroblasts via inhibition of MMP expression 31) but only a few plant-derived compounds, such as obovatol, have been reported to stimulate collagen synthesis. 21) Our results suggest that spinasterol-Glc may stimulate expression of proa1 (I) and/or proa2 (I) genes in fibroblast cells.…”

10‐Hydroxy‐2‐decenoic acid prevents ultraviolet A‐induced damage and matrix metalloproteinases expression in human dermal fibroblasts

“…2a). This result indicates that the inhibitory effect of 10‐HDA on MMP‐1 and MMP‐3 expression is not related to non‐specific cytotoxicity, as previously reported 32 …”

Ultraviolet B‐induced matrix metalloproteinase‐1 and ‐3 secretions are mediated via PTEN/Akt pathway in human dermal fibroblasts

“…1B,C, 2C) is quite different from PTEN‐mediated regulation of MMP‐2 in glioma cells. However, no induction of MMP‐2 in fibroblasts upon UV irradiation has been reported by other groups (Fisher et al, 1996; Kawaguchi et al, 1996; Kut et al, 1997; Moon et al, 2005), implying that the regulation of MMP‐2 may not be mediated by PTEN in fibroblasts. This conclusion is also supported by our results showing that the transfection of PTEN genes did not affect MMP‐2 secretion (data not shown).…”