Psoriasis is a skin disease that affects millions of individuals. Genetic risk factors for psoriasis include a common deletion of two late cornified envelope (LCE) genes (LCE3B and LCE3C) located within a cluster of genes expressed during epithelial differentiation and skin repair. It was previously discovered that treatment with 1,25-dihydroxyvitamin…
Psoriasis is a skin disease that affects millions of individuals. Genetic risk factors for psoriasis include a common deletion of two late cornified envelope (LCE) genes (LCE3B and LCE3C) located within a cluster of genes expressed during epithelial differentiation and skin repair. It was previously discovered that treatment with 1,25-dihydroxyvitamin D3 (1,25D) or analogs thereof can improve psoriasis symptoms in many patients, but the molecular mechanisms for this action are largely unknown. Our laboratory previously showed that 1,25D as well as low affinity ligands for the vitamin D receptor (VDR), such as delphinidin and cyanidin, are capable of upregulating the remaining LCE3A, -3D, and -3E genes to potentially compensate for the loss of LCE3B and -3C in promoting skin repair. In the current study, DHA and curcumin were tested and found to also upregulate LCE3 transcripts in a dose-dependent manner. To investigate other potential target genes for 1,25D and DHA, we tested JunB, for which low or absent expression has been reported to cause or be associated with psoriatic lesions. Our experiments showed a trend for an upregulation of JunB mRNA after DHA treatment, potentially providing benefit for psoriasis patients. Although our hypothesis is that DHA functions as a vitamin D receptor ligand to mediate upregulation of JunB and LCE3 genes, other investigators have assumed that DHA actions in skin are mediated via PPAR isoforms. We therefore utilized a selective ligand for PPAR delta (GW501516) to determine whether PPAR delta, the primary PPAR isoform in keratinocytes, is a mediator of DHA-induced LCE3 gene activation. Although a modest upregulation of LCE3 genes was seen after treatment with GW501516, our findings are still consistent with DHA acting primarily as a VDR ligand. Our results not only provide additional information about the ability of VDR ligands to upregulate specific skin genes with relevance for skin repair, but also may help provide a molecular basis for testing improved treatments for mild to moderate psoriasis.
Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty…
Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate. Hayflick used his research on normal embryonic cells to develop a vaccine for polio, and from HayflickÕs published directions, scientists developed vaccines for rubella, rabies, adenovirus, measles, chickenpox and shingles.
Although best known for his work with the fruit fly, for which he earned a Nobel Prize and the title "The Father of Genetics," Thomas Hunt Morgan's contributions to biology reach far beyond genetics. His research explored questions in embryology, regeneration, evolution, and heredity, using a variety of approaches.
