Abstract

- D3 regulates keratinocyte differentiation and proliferation, but the precise mechanisms by which it does so are not well defined and the outcomes appear to be dependent on experimental conditions including the presence of growth factors. Calcium and protein kinase C (PKC) also regulate keratinocyte differentiation, and are likely to modulate these actions of D3. D3 induces the phospholipase C (PLC) family, enzymes which cleave phosphatidyl inositol bis phosphate (PIP2) into diacylglycerol (DAG) and inositol tris phosphate (1P3). These second messengers activate PKC and increase intracellular calcium (Cai). PLCg-1 is the most abundant member of the PLC family in keratinocytes, is regulated by calcium as well as D3, and is unique within the PLC family in its interaction with growth factor receptors such as EGFR and NGFR (trk). These characteristics have led the investigators to propose the following hypothesis. PLCg-l plays a critical role in the interaction between D3 and selected growth factors in their regulation of keratinocyte proliferation and differentiation. Dr. Bikle will test this hypothesis by achieving the following two objectives: 1. Determine the role of PLCg-1 in mediating the ability of D3 to regulate proliferation and differentiation. This will be accomplished by altering the production or activity of PLCg-1 in the cell and evaluating the effect of such maneuvers on the ability of D3 to regulate proliferation and differentiation. 2. determine whether the interaction between D3 and the growth factors EGF and NGF requires PLCg. To achieve this aim the ability of EGF and NGF to modulate the effect of D3 on proliferation and differentiation will be tested, the impact of induction of PLCg-1 by D3 on the acute effects of EGF and NGF with respect to increased Cai and PKC activity will be determined, and the requirement for PLCg-1 in the interactions between D3 and the growth factors EGF and NGF with respect to proliferation and differentiation will be evaluated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR038386-13
Application #
6511685
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
1987-05-01
Project End
2004-03-31
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
13
Fiscal Year
2002
Total Cost
$266,324
Indirect Cost

  Institution

Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121

  Publications

Jassil, Navinder K; Sharma, Anupa; Bikle, Daniel et al. (2017) VITAMIN D BINDING PROTEIN AND 25-HYDROXYVITAMIN D LEVELS: EMERGING CLINICAL APPLICATIONS. Endocr Pract 23:605-613
Xie, Zhongjian; Yuan, Yuan; Jiang, Yi et al. (2017) p120-Catenin Is Required for Dietary Calcium Suppression of Oral Carcinogenesis in Mice. J Cell Physiol 232:1360-1367
Bikle, Daniel; Bouillon, Roger; Thadhani, Ravi et al. (2017) Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status? J Steroid Biochem Mol Biol 173:105-116
Bikle, Daniel D (2017) Vitamin D Prevents Sunburn: Tips for the Summer? J Invest Dermatol 137:2045-2047
Malmstroem, Sofie; Rejnmark, Lars; Imboden, John B et al. (2017) Current Assays to Determine Free 25-Hydroxyvitamin D in Serum. J AOAC Int 100:1323-1327
Bikle, Daniel D; Malmstroem, Sofie; Schwartz, Janice (2017) Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol Metab Clin North Am 46:901-918
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Elias, Peter M; Williams, Mary L; Bikle, Daniel D (2016) The vitamin D hypothesis: Dead or alive?: Response to Dr. William Grant's ""The UVB-vitamin D3-pigment hypothesis is alive and well-AJPA-2016-00237"". Am J Phys Anthropol 161:756-757
Bikle, Daniel D (2016) The Endocrine Society Centennial: Extrarenal Production of 1,25 Dihyroxyvitamin D Is Now Proven. Endocrinology 157:1717-8
Mady, Leila J; Ajibade, Dare V; Hsaio, Connie et al. (2016) The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle. J Invest Dermatol 136:1337-1345

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