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.