Background: Accumulation of epidermal hyaluronan is an early event in UVB-induced squamous cell carcinomas. Results: UVB increases keratinocyte hyaluronan synthesis by up-regulating hyaluronan synthases Has1 and -2 via p38 and Has3 via Ca 2ϩ /calmodulin-dependent protein kinase II (CaMKII) signaling. Conclusion: UVB triggers deposition of epidermal hyaluronan through at least two signaling pathways. Significance: Increased hyaluronan synthesis is an inherent feature of keratinocyte adaptation to radiation injury.

The data show that rClca2 is a novel UVB target gene and suggest that it might play a role in epidermal differentiation and UV-dependent skin malignancies.