Molecular basis of sun-induced premature skin ageing and retinoid antagonism

Abstract

Damage to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation, and is believed to be responsible for the wrinkled appearance of sun-exposed skin. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).

Naringenin targets ERK2 and suppresses UVB‐induced photoaging

“…Matrix metalloproteinase‐1 acts as a major mediator of UV‐induced photoaging by degrading the collagen in human skin 1, 3. Therefore, if specific natural phytochemicals suppress UV‐induced MMP‐1 expression, they could be promising anti‐photoaging agents.…”

Tissue elasticity and the ageing elastic fibre

“…Although up-regulation of ECM protease expression is a unifying feature of age-related inflammatory conditions such as emphysema (Robbesom et al 2008), atherosclerosis (Robert et al 2008) and UVinduced photoageing (Fisher et al 1996), the constitutive expression of MMPs in non-inflamed lung, aorta and skin (Chen et al 2005;McNulty et al 2005;Meyer et al 1998) may be sufficient, given the longevity of ECM assemblies, to gradually degrade proteins over many years. To date, eight MMPs have been shown to degrade elastic fibre proteins in vitro: insoluble elastin is degraded to soluble fragments by MMP-2, -7, -9, -10, -12 and -14 (Chakraborti et al 2003;Taddese et al 2008), whilst fibrillin microfibrils and peptides are catabolised by MMP-2,-3,-9,-12 and -13 (Ashworth et al 1999;Tsuruga et al 2007).…”

“…Exposure of skin or skin-derived cells to UVR, for example, is known to upregulate the expression of many elastic fibre degrading enzymes, including MMP-2, -3, -9, -12 and -13 and the serine protease neutrophil elastase (Fisher et al 1996;Kim et al 2006;Rijken et al 2005;Saarialho-Kere et al 1999). ROS generation may mediate elastic fibre damage in skin either indirectly, via protease upregulation (Yaar and Gilchrest 2007), or directly via interaction with the sulphur containing amino acids methionine and cysteine (Haenold et al 2005).…”

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

“…Ultraviolet radiation, in particular UVB with a wavelength range between 290 and 320 nm, represents one of the most important environmental factors because of its health hazardous effects, which include induction of skin cancer (Armstrong and Kricker, 2001), suppression of the immune system (Beissert and Schwarz, 1999) and chronic skin damage (Fisher et al, 1996). The biological effects of UV are multiple and include the release of soluble mediators, alterations of surface molecule expression and the induction of apoptosis.…”