Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human dermal fibroblast cells

Background: Chronic exposure to ultraviolet (UV) radiation (mainly UVA) induces a sustained increase of matrix metalloproteinases (MMPs), especially MMP1, MMP2, MMP3 and MMP9 in human skin fibroblasts. MMPs can lead to the degradation of fibrous connective tissue, which is the main cause of skin photoageing. The molecular mechanisms through which fibroblasts sense UVA and trigger the cell signalling pathways involved in the upregulation of MMPs have not been well elucidated.

Objectives: Here, we investigated the function and potential mechanisms of photoageing of opsin (OPN)3 in normal human dermal fibroblasts (NHDFs).

Methods: Real-time polymerase chain reaction and Western blot analysis were used to analyse the expression levels of OPN3 in NHDFs and photoageing models. Subsequently, NHDFs transfected with OPN3 inhibitors and indicators related to photoageing before and after UVA irradiation included expression levels of MMP1, MMP2, MMP3 and MMP9, and signalling pathway protein molecules were examined.

Results: We provide evidence that OPN3 initiates UVA phototransduction in NHDFs. OPN3 triggers phosphorylation of activator protein 1 and ultimately upregulates MMP1, MMP2, MMP3 and MMP9 in NHDFs through activating Ca²⁺ /calmodulin-dependent protein kinase II, cyclic adenosine monophosphate response element-binding protein, extracellular signal-regulated kinase, c-JUN N-terminal kinase and p38. Here, we demonstrate for the first time that OPN3 is the key sensor responsible for upregulating MMP1, MMP2, MMP3 and MMP9 in NHDFs following UVA exposure via the calcium-dependent G protein-coupled signalling pathway.

Conclusions: Our studies provide insights into the understanding of the molecular mechanisms through which human skin cells respond to UVA radiation and may reveal molecular targets for skin photoageing prevention or clinical management. What's already known about this topic? Photoaged fibroblasts accumulate with long-term ultraviolet (UV) exposure. Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of photoageing. MMP1, MMP2, MMP3 and MMP9 are responsible for the destruction of fibroblast collagen in severely photodamaged skin. Opsins (OPNs) are light-sensitive members of the superfamily of heptahelical G protein-coupled receptors, a family of cell surface receptors that are activated by a variety of stimuli and mediate signalling across membranes. What does this study add? OPN3 is highly expressed in fibroblasts and responds to UVA irradiation. OPN3 regulates the expression of MMP1, MMP2, MMP3 and MMP9 via the calcium-dependent G protein-coupled signalling pathway. OPN3 is a light-sensitive sensor that plays an important role in photoageing of the skin.