000135414 001__ 135414
000135414 005__ 20181203021520.0
000135414 022__ $$a0022-202X
000135414 02470 $$2PMID$$a12485431
000135414 0247_ $$2doi$$a10.1046/j.1523-1747.2002.19605.x
000135414 037__ $$aARTICLE
000135414 245__ $$aRole of peroxisome proliferator-activated receptor alpha in epidermal development in utero
000135414 269__ $$a2002
000135414 260__ $$c2002
000135414 336__ $$aJournal Articles
000135414 520__ $$aThe protective function of the skin is mediated by the stratum corneum, the outermost layer of the skin, which is the end-product of epidermal differentiation. Previously, we showed that fetal rat skin explants complete the late-stage milestones of epidermal development when grown in a serum- and growth-factor-free medium, suggesting that endogenous metabolites could regulate the late program that leads to barrier formation. Because a variety of endogenous free fatty acids are known activators, peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a potential candidate for this key regulatory role. Indeed, whereas PPAR-alpha expression is first noted at gestational day 13.5 and peaks between days 14.5 and 15.5, fatty acid synthesis is very active in fetal rodent epidermis peaking at gestational day 17. Furthermore, we have reported that both epidermal differentiation and stratum corneum formation in utero are stimulated by pharmacologic activation of PPAR-alpha. This study was designed to test whether PPAR-alpha plays a physiologic role in epidermal differentiation and stratum corneum formation in utero. In PPAR-alpha-/- mice we observed delayed stratum corneum formation between day 18.5 of gestation and birth. Concurrently, there was diminished beta-glucocerebrosidase activity at the stratum granulosum-stratum corneum junction and a modest decrease in both involucrin and loricrin protein expression, markers of keratinocyte differentiation. Both the number of stratum corneum cell layers was reduced and the processing of the lamellar bilayers was delayed in animals lacking PPAR-alpha, indicating a transient functional defect. In contrast, the lamellar body secretory system as well as rates of epidermal proliferation and cell death appeared normal in PPAR-alpha-/- mice. These results indicate that PPAR-alpha plays a physiologic role during fetal stratum corneum development. The transient and incomplete nature of the developmental delay, however, is consistent with regulation of the late stages of epidermal development by multiple factors.
000135414 700__ $$aSchmuth, Matthias
000135414 700__ $$0240041$$aSchoonjans, Kristina$$g183105
000135414 700__ $$aYu, Qian-Chun
000135414 700__ $$aFluhr, Joachim W.
000135414 700__ $$aCrumrine, Debra
000135414 700__ $$aHachem, Jean-Pierre
000135414 700__ $$aLau, Peggy
000135414 700__ $$0240040$$aAuwerx, Johan$$g185233
000135414 700__ $$aElias, Peter M.
000135414 700__ $$aFeingold, Kenneth R.
000135414 773__ $$j119$$k6$$q1298-303$$tThe Journal of investigative dermatology
000135414 909C0 $$0252023$$pNCEM$$xU11905
000135414 909C0 $$0252495$$pUPSCHOONJANS$$xU12735
000135414 909CO $$ooai:infoscience.tind.io:135414$$pSV$$particle
000135414 917Z8 $$x182396
000135414 937__ $$aNCEM-ARTICLE-2002-006
000135414 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000135414 980__ $$aARTICLE