Abstract

In the epidermis sphingolipids are concentrated in the upper, differentiated cell layers. Although substantial evidence supports a critical role for sphingolipids in the providion of the permeability barrier, little is known about the regulation of spingolipid biosynthesis in the epidermis. Cultured human keratinocytes should provide a useful model to study the link between spingolipid biosynthesis and epidermal differentiation because these cultures, when grown at an air-medium interface, display advanced morphologic differentiation, as well as increased spingolipid content and biosynthesis in comparison to parallel immersed cultures. In this proposal we will test the following: 1. Sphingolipid composition and synthesis by keratinocytes varies in relation to their degree of differentiation. 2. Products of sphingolipid metabolism may themselves regulate epidermal differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR039448-07
Application #
3747906
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling et al. (2015) Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer. J Steroid Biochem Mol Biol 148:47-51
Bikle, Daniel D (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319-29
Bikle, Daniel D (2014) Vitamin D and cancer: the promise not yet fulfilled. Endocrine 46:29-38
Bikle, Daniel D (2014) The vitamin D receptor: a tumor suppressor in skin. Adv Exp Med Biol 810:282-302
Tu, Chia-Ling; Bikle, Daniel D (2013) Role of the calcium-sensing receptor in calcium regulation of epidermal differentiation and function. Best Pract Res Clin Endocrinol Metab 27:415-27
Jiang, Yan J; Kim, Peggy; Uchida, Yoshikazu et al. (2013) Ceramides stimulate caspase-14 expression in human keratinocytes. Exp Dermatol 22:113-8
Tu, Chia-Ling; Crumrine, Debra A; Man, Mao-Qiang et al. (2012) Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol 132:2350-2359
Bikle, Daniel D (2012) Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord 13:3-19
Bourguignon, L Y W; Earle, C; Wong, G et al. (2012) Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene 31:149-60

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