Vitamin D, Resveratrol, and Control of LCE3 Genes with Implications for Psoriasis

Persistent Link:
http://hdl.handle.net/10150/603561
Title:
Vitamin D, Resveratrol, and Control of LCE3 Genes with Implications for Psoriasis
Author:
Batie, Shane
Affiliation:
The University of Arizona College of Medicine - Phoenix
Issue Date:
23-Mar-2016
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Collection Information:
This item is part of the College of Medicine - Phoenix Scholarly Projects 2016 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
Publisher:
The University of Arizona.
Abstract:
Psoriasis (Psx) is a chronic inflammatory skin disease with abnormal keratinocyte proliferation and differentiation. One genetic risk factor for psoriasis (denoted PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in terminally differentiated keratinocytes. Analogs of the hormonal form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25D) are routinely used to treat Psx, a skin disease that affects over 7 million patients in the US. However, this therapy, even when combined with an anti‐inflammatory (e.g., betamethasone), is ineffective in some patients, particularly those with a severe disease phenotype, underscoring the need for better agents. Further, the mechanism of action of vitamin D analogs is not understood, although their ability to reduce proliferation and promote differentiation of psoriatic keratinocytes is both valued in therapy and is complementary to anti‐inflammatory agents. Given that 1,25D acts via the vitamin D receptor (VDR) to regulate gene expression, this project is focused on elucidating expression alterations in psoriasisrelevant genes mediated by the 1,25D‐liganded VDR in human keratinocytes. Whereas VDR activity is increased when bound to 1,25D, less is known about the ability of other nutritionallyderived lipids to act on VDR. The current study is designed to: 1) evaluate resveratrol, an antioxidant found in the skin of red grapes, as an effector of VDR signaling and potent activator of LCE gene transcription in human keratinocytes, and 2) determine whether resveratrol acts synergistically with 1,25D to regulate the expression of LCE3 genes, with the potential to boost skin repair and ameliorate the symptoms of psoriasis.
MeSH Subjects:
Vitamin D; Psoriasis
Description:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Mentor:
Whitfield, G. Kerr PhD

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleVitamin D, Resveratrol, and Control of LCE3 Genes with Implications for Psoriasisen_US
dc.contributor.authorBatie, Shaneen
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen
dc.date.issued2016-03-23en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2016 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.publisherThe University of Arizona.en
dc.description.abstractPsoriasis (Psx) is a chronic inflammatory skin disease with abnormal keratinocyte proliferation and differentiation. One genetic risk factor for psoriasis (denoted PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in terminally differentiated keratinocytes. Analogs of the hormonal form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25D) are routinely used to treat Psx, a skin disease that affects over 7 million patients in the US. However, this therapy, even when combined with an anti‐inflammatory (e.g., betamethasone), is ineffective in some patients, particularly those with a severe disease phenotype, underscoring the need for better agents. Further, the mechanism of action of vitamin D analogs is not understood, although their ability to reduce proliferation and promote differentiation of psoriatic keratinocytes is both valued in therapy and is complementary to anti‐inflammatory agents. Given that 1,25D acts via the vitamin D receptor (VDR) to regulate gene expression, this project is focused on elucidating expression alterations in psoriasisrelevant genes mediated by the 1,25D‐liganded VDR in human keratinocytes. Whereas VDR activity is increased when bound to 1,25D, less is known about the ability of other nutritionallyderived lipids to act on VDR. The current study is designed to: 1) evaluate resveratrol, an antioxidant found in the skin of red grapes, as an effector of VDR signaling and potent activator of LCE gene transcription in human keratinocytes, and 2) determine whether resveratrol acts synergistically with 1,25D to regulate the expression of LCE3 genes, with the potential to boost skin repair and ameliorate the symptoms of psoriasis.en
dc.typeThesisen
dc.subject.meshVitamin Den
dc.subject.meshPsoriasisen
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en
dc.contributor.mentorWhitfield, G. Kerr PhDen
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