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HaCaT cell line as a model system for vitamin D-3 metabolism in human skin


, : HaCaT cell line as a model system for vitamin D-3 metabolism in human skin. Journal Of Investigative Dermatology. 108(1): 78-82

Synthesis and catabolism of calcitriol (1,25(OH)-2D-3) were studied using HaCaT cell line as a cell culture model. Our results indicate that stimulation of HaCaT cells with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) within 16 h just prior to reaching confluence amplified the production of calcitriol when calcidiol (3H-25OHD-3) was used as a substrate. EGF- and TGF-alpha-induced (0.1-10 nM) 1-hydroxylation of 3H-25OHD-3 was concentration-dependent but showed different kinetics. Synthesis of calcitriol induced by EGF was inversely related to the degree of cellular confluence. Stimulation by EGF was an actinomycin D- and cycloheximide-sensitive process. Independently of the growth factor used, the production of 3H-24R,25(OH)-2D-3 and the catabolism of 3H-1,25(OH)-2D-3 to 3H-1,24,25(OH)-2D-3 were unexpectedly low ( ltoreq 5% and ltoreq 2%), as compared to the amount of calcitriol generated. Exogenous addition of unlabeled 1,25(OH)-2D-3, 1,24R(OH)-2D-3, calcipotriol, or 24R,25(OH)-2D-3, at concentrations as low as 10-11 M, potently inhibited the 3H-1,25(OH)-2D-3 production. These results suggest that EGF-treated HaCaT keratinocytes could serve for further studies of the vitamin D-3 pathway and its relationship to proliferation and differentiation, but differences in calcitriol synthesis and catabolism from those in cultured primary keratinocytes or other cell lines must be considered.

US$19.90

PMID: 8980292

DOI: 10.1111/1523-1747.ep12285640


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