CD98hc is a highly glycosylated transmembrane protein encoded by the slc3a2 gene. Two isoforms have been described in mice (via genome sequencing). Alternative ATGs seem to generate these 2 isoforms, for which specific functions are unknown. CD98hc protein is a dual function protein: i) modulating integrins signaling, specifically mechanotransduction; ii) and regulating SLC7 amino acid transporter family, thereby regulating cellular metabolism. In skin, CD98hc is expressed in both basal keratinocytes and dermal fibroblasts. As such, it is necessary for maintaining skin homeostasis. Importantly, CD98hc expression wanes with age. With ultraviolet (UV) exposure and aging, skin softens due to major changes in the dermal extracellular matrix (collagens and elastin modification). Thus, we are currently deciphering the effect of UVs on the expression of CD98hc in skin cells. To do so, we define how CD98hc isoforms expression is impacted by 1- tissue stiffness (using substrate equivalent of young/stiff (4kPa) and elderly/soft (1 kPa) skin) and 2- UV exposure. Finally, we decipher the molecular mechanisms involved and if a specific function for each isoform can be identified. We now show, thanks to lysates deglycosylation, that both CD98hc isoforms exist and are expressed in the keratinocytes and dermal fibroblasts. Then, by seeding murine dermal fibroblast on 4kPa and 1kPa, we find that the isoforms of CD98hc are differentially regulated on young/stiff substrate. As expected, the expression of both isoforms is lost on a stiffness mimicking an elderly murine skin. We also demonstrate that UV exposure (200J/m2 eq UVB) of the murine dermal fibroblasts seem to differentially regulate the 2 isoforms. To understand the function of the two isoforms of CD98hc upon UV exposure, we are now cloning them to be able to express them separately in CD98hc KO murine dermal fibroblasts. Our work will provide novel insight on skin physiology during aging and UV exposure.

ESDRLB024 - Impact of UVs on the expression of CD98hc, a regulator of skin homeostasis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING