Alteration of the TGF-beta/SMAD pathway in intrinsically and UV-induced skin aging.

In an effort to characterize transforming growth factor (TGF-beta) signaling and to determine its association with the aging and photoaging processes, we directly compared the expressions of TGF-beta/SMAD in intrinsically aged and photoaged human skin in vivo. By using an RNase protection assay and by immunohistochemistry, we found that the expression levels of TbetaRII mRNA and protein in the epidermis of the forearm (sun-exposed) of the elderly were significantly lower than that of the upper-inner arm (sun-protected) skin of the same individual. In the epidermis, the expressions of Smad7 mRNA in both the intrinsically aged and photoaged skin of the elderly were higher than in the sun-protected skin of the young, and this was elevated in the photoaged epidermis. Decreased pSmad2 immunoreactivity was observed in the epidermis of photoaged forearm skin versus matched intrinsically aged skin. This decrease was also found in the epidermis of upper-inner arm skin of the elderly versus the young. These results suggest that the UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2.