Fibroblasts Behavior after N-Acetylcysteine and Amino Acids Exposure: Extracellular Matrix Gene Expression

Abstract

Reactive oxygen species (ROS) are chemically reactive molecules with impaired electrons that make them unstable and able to react easily with a great variety of molecules. The main targets of ROS are DNA, proteins, and membrane phospholipids. In the skin, ROS are able to affect the production of collagen and elastin, the main components of the extracellular matrix (ECM). This action contributes to the skin's aging. N-Acetylcysteine (NAC) is an acetylated cysteine residue with excellent anti-oxidant activity that boosts glutathione (GSH) levels. This study evaluates the effect of a solution of NAC and amino acids, which is used in aesthetic medicine as an intra-dermal injective treatment, on fibroblast behavior. To this aim, the expression levels of some ECM-related genes (HAS1, HYAL1 ELN, ELANE, MMP2, MMP3, MMP13, COL1A1, COL3A1) were analyzed on cultured dermal fibroblasts using real-time reverse transcription polymerase chain reaction (RT-PCR). All but two collagen genes were up-regulated after 24 hr of treatment.

NRF2 Shortage in Human Skin Fibroblasts Dysregulates Matrisome Gene Expression and Affects Collagen Fibrillogenesis

“…Altogether our data underscores the critical role for NRF2 in regulating matrisome expression and the need of a strict NRF2 balance for a healthy dermal ECM. Finally, as oxidative stress also regulates ECM gene expression (Avantaggiato et al, 2014;Spadoni et al, 2015), our data provide evidence that, in addition to stress-induced NRF2 targets, basal targets participate in the regulation of ECM gene expression.…”

“…As oxidative stress was reported to affect ECM gene expression (Avantaggiato et al, 2014;Spadoni et al, 2015), ROS levels were measured in our samples that exclude redox imbalance due to possible transfection stress (supplementary Figure S3a). In addition, RNA-seq expression levels of known ROS-induced genes SOD1, SOD2, SOD3 (encoding super oxide dismutases) and NOX4 (NADPH oxidase 4) (St-Pierre et al, 2006;Murphy-Marshman et al, 2017), were unchanged in all conditions (supplementary Figure S3b).…”

Post-Translational Modifications Evoked by Reactive Carbonyl Species in Ultraviolet-A-Exposed Skin: Implication in Fibroblast Senescence and Skin Photoaging

“…N-acetyl cysteine and may increase the GSH content [ 119 ]. When added to skin fibroblasts, N-acetyl cysteine enhances the expression of ECM genes [ 120 ]. In vivo , topical pretreatment with N-acetyl cysteine protects against skin-aging evoked by high or low UV-A radiation in hairless mice [ 121 ].…”