Opsin 5 is a key regulator of ultraviolet radiation-induced melanogenesis in human epidermal melanocytes

Background: Human skin, which is constantly exposed to solar ultraviolet radiation (UVR), has a unique ability to respond by increasing its pigmentation in a protective process driven by melanogenesis in human epidermal melanocytes (HEMs). However, the molecular mechanisms used by HEMs to detect and respond to UVR remain unclear.

Objectives: To investigate the function and potential mechanism of opsin 5 (OPN5), a photoreceptor responsive to UVR wavelengths, in melanogenesis in HEMs.

Methods: Melanin content in HEMs was determined using the NaOH method, and activity of Tyrosinase (TYR) (a key Enzyme in melanin synthesis) was determined by the l-DOPA method. OPN5 expression in UVR-treated vs. untreated HEMs and explant tissues was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence. Short interfering RNA-mediated OPN5 knockdown and a lentivirus OPN5 overexpression model were used to examine their respective effects on TYR, tyrosinase-related protein 1 (TRP1), TRP2 and microphthalmia-associated transcription factor (MITF) expression, under UVR. Changes in expression of TYR, TRP1 and TRP2 caused by changes in OPN5 expression level were detected by RT-qPCR and Western blot. Furthermore, changes in signalling pathway proteins were assayed.

Results: We found that OPN5 is the key sensor in HEMs responsible for UVR-induced melanogenesis. OPN5-induced melanogenesis required Ca²⁺ -dependent G protein-coupled receptor- and protein kinase C signal transduction, thus contributing to the UVR-induced MITF response to mediate downstream cellular effects, and providing evidence of OPN5 function in mammalian phototransduction. Remarkably, OPN5 activation was necessary for UVR-induced increase in cellular melanin and has an inherent function in melanocyte melanogenesis.

Conclusions: Our results provide insight into the molecular mechanisms of UVR sensing and phototransduction in melanocytes, and may reveal molecular targets for preventing pigmentation or pigment diseases.