Upregulation of MMP12 and Its Activity by UVA1 in Human Skin: Potential Implications for Photoaging

Abstract

UVA1 constitutes around 75% of the terrestrial UV radiation, and most of the output of artificial tanning sources. However, the molecular effects of UVA1 in human skin in vivo are surprisingly poorly understood. We have examined time-dependent whole-genome expression, along with mRNA and protein changes in the skin after one minimal erythema dose of spectrally pure UVA1 (50 J cm(-2)) and 300 nm UVB (30 mJ cm(-2)). After 24 hours, the genes induced to the greatest extent were those involved in extracellular matrix remodeling with both UVA1 (P=5.5e-7) and UVB (P=2.9e-22). UVA1 and UVB caused different effects on matrix metalloproteinase (MMP) expression: UVB induced MMP1, MMP3, and MMP10 mRNA at 24 hours to a much greater extent than UVA1. MMP12 induction by UVA1 at 6 hours is marked and much greater than that by UVB. We have found that MMP12 mRNA induction by UVA1 resulted in expression of MMP12 protein, which is functional as an elastase. This induction of elastase activity did not occur with UVB. We hypothesize that the UVA1 induction of MMP12 mediates some of its photoaging effects, particularly by contributing to elastin degeneration in late solar elastosis. MMP12 is a good marker of UVA1 exposure.

Restoration of Mitochondrial Integrity, Telomere Length, and Sensitivity to Oxidation by In Vitro Culture of Fuchs' Endothelial Corneal Dystrophy Cells

“…9,10,46,47 UVA wavelengths were used in this experiment because they represent 75% of the terrestrial UV radiations, they are known to reach the corneal endothelium, and they efficiently induce ROS. [6][7][8]48 H 2 O 2 , an oxidizing component induced by the mitochondrial respiratory chain, was also used to assess sensitivity to oxidative stress. Both UVA-and H 2 O 2 -induced cell death methods showed that FECD and healthy cultured cells behave similarly in the presence of oxidative stress (Fig.…”

UVA‐1 exposure in vivo leads to an IL‐6 surge within the skin

“…It is a clear promotor of skin ageing by induction of matrix degrading metalloproteases (MMPs) and of skin cancer by induction of photochemical DNA mutations such as cyclopyrimidine dimers (CPD). [1,2] UVA-1 is also the main waveband used by the sunbed manufacturers, as it induces a suntan. The effects of UVA-1 on human skin are clinically evaluated by the pigmentation it induces at doses below the erythema threshold.…”

Sistemas nanoestruturados contendo o óleo da polpa e da amêndoa da bocaiuva (<i>Acrocomia aculeata</i>) (Jacq.) Lodd. xx Mart.): preparação e caracterização físico-química

“…Existem muitas vias que conduzem ao fotoenvelhecimento e esses mecanismos ainda não são muito bem elucidados, porém, sabe-se que a formação de espécies reativas de oxigênio (radicais livres), a indução de metaloproteinases na matriz e o fato de crescimento (TGF-β) refletem aspectos centrais do envelhecimento da pele DOREN, 2015;PITTAYAPRUEK et al,2016;IMOKAWA & ISHIDA, 2015;NEWTON et al,2015;REHMAN, KONDO & SHIMIZU, 2015;TEWARI et al, 2014;LESIAK et al, 2016).…”

“…A matriz extracelular é composta principalmente de colágeno I e III, elastina, proteoglicanos e fibronectina. Na pele exposta à radiação UV, podese observar a desorganização das fibras de colágeno, aumento da produção de elastina com depósitos prejudiciais, diminuição da quantidade de colágenio I e III e a junção dermoepidérmica é achatada, além de sua função também ser afetada DOREN, 2015;PITTAYAPRUEK et al,2016;IMOKAWA & ISHIDA, 2015;NEWTON et al,2015;REHMAN, KONDO & SHIMIZU, 2015;TEWARI et al, 2014;LESIAK et al, 2016).…”

“…As metaloproteinases de matriz (MMPs) são enzimas proteolíticas que têm a capacidade para degradar o colágeno, fibras elásticas e outras proteínas localizadas dentro do tecido conjuntivo. A sua atividade biológica é modulada principalmente por inibidores tecidulares de metaloproteinases de matriz (TIMP) DOREN, 2015;PITTAYAPRUEK et al,2016;IMOKAWA & ISHIDA, 2015;NEWTON et al,2015;REHMAN, KONDO & SHIMIZU, 2015;TEWARI et al, 2014;LESIAK et al, 2016;HAAKE et al,2004) …”