Effects of Retinoic Acid on Wingless (WNT) Signaling in the Hair Follicles of Mice
WNT/N-catenin signaling is important in determining stem cell fate during the hair cycle, and regulates whether sebaceous glands or hair follicles are formed (Merrill et al., 352001; Fuchs and Horsley, 2008). When aberrant WNT/N-catenin signaling is inhibited in the sebaceous gland (but not other areas of the hair follicle), hair follicles form from those cells. However, aberrantly induced WNT/N-catenin signaling in the sebaceous gland leads to proliferation of sebocytes at the expense of hair follicle formation. As we observed WNT signaling in the sebaceous gland and some bulge cells of dorsal skin when RA was not present, this implies that RA normally regulates and inhibits WNT/N-catenin signaling in these areas of the hair follicle. This implication is supported by a previous study, whichfound that retinoic acid decreased the activity of the N-catenin-LEF/TCF signaling pathway, a key component of the WNT signaling pathway in MCF7 breast cancer cells, retinoidsensitive adenomatous polyposis coli (APC)-mutant colon cancer (Caco-2) and retinoidsensitive APC-mutant human colon adenocarcinoma grade II (HT29) cells (Easwaran et al., 1999). One implication for aberrant WNT/ɴ-catenin signaling is that many tumors andcancers in the skin and body, as well as acne, arise from aberrant sebocyte proliferation(Widelitz, 2004; Fodde and Brabletz, 2007; Slavik et al., 2007; Gehrke et al., 2009; Zoubuoulis, 2004). Components of the WNT/ B-catenin signaling pathway may therefore serve as targets of cancer treatments (Easwaran et al., 1999; Luu, 2004; Widelitz 2004). Our 3 preliminary studies indicate that RA does indeed interact with WNT signaling in the hair follicle, and inhibition of RA increases WNT signaling in the sebaceous gland. Further studies may help us better understand the quantity of RA needed to regulate WNT signaling in the hair follicle, thus preventing cancer and allowing for hair follicle formation.