Stan, FXR is a receptor involved in cholesterol activity (farnesoid X-activated Receptor). It is a member of a super gene family that includes many of the recptors that LGND targets and it also forms heterodimers with RXRs (as does PPAR alpha for fatty acid syntesis and PPAR gamma for insulin reisitance):
Here's an abstract with more info:
J Clin Invest 1997 Aug 1;100(3):705-712
Activators of the nuclear hormone receptors PPARalpha
and FXR accelerate the development of the fetal epidermal
permeability barrier.
Hanley K, Jiang Y, Crumrine D, Bass NM, Appel R, Elias PM, Williams ML, Feingold
KR
Department of Dermatology, University of California, San Francisco, California 94143, USA.
Members of the superfamily of nuclear hormone receptors which are obligate heterodimeric partners
of the retinoid X receptor may be important in epidermal development. Here, we examined the
effects of activators of the receptors for vitamin D3 and retinoids, and of the peroxisome proliferator
activated receptors (PPARs) and the farnesoid X-activated receptor (FXR), on the development of
the fetal epidermal barrier in vitro. Skin explants from gestational day 17 rats (term is 22 d) are
unstratified and lack a stratum corneum (SC). After incubation in hormone-free media for 3-4 d, a
multilayered SC replete with mature lamellar membranes in the interstices and a functionally
competent barrier appear. 9-cis or all-trans retinoic acid, 1,25 dihydroxyvitamin D3, or the
PPARgamma ligands prostaglandin J2 or troglitazone did not affect the development of barrier
function or epidermal morphology. In contrast, activators of the PPARalpha, oleic acid, linoleic acid,
and clofibrate, accelerated epidermal development, resulting in mature lamellar membranes, a
multilayered SC, and a competent barrier after 2 d of incubation. The FXR activators, all-trans
farnesol and juvenile hormone III, also accelerated epidermal barrier development. Activities of
beta-glucocerebrosidase and steroid sulfatase, enzymes previously linked to barrier maturation, also
increased after treatment with PPARalpha and FXR activators. In contrast, isoprenoids, such as
nerolidol, cis-farnesol, or geranylgeraniol, or metabolites in the cholesterol pathway, such as
mevalonate, squalene, or 25-hydroxycholesterol, did not alter barrier development. Finally, additive
effects were observed in explants incubated with clofibrate and farnesol together in suboptimal
concentrations which alone did not affect barrier development. These data indicate a putative
physiologic role for PPARalpha and FXR in epidermal barrier development. |
