Abstract

Collagen is the major structural protein in the body and one that plays an important role in such diverse biological functions as differentiation, remodeling, wound repair, and aging. Human skin fibroblasts in culture devote a large portion of their protein synthetic capacity to collagen, thus providing a convenient system for studying regulation of collagen synthesis. Our ongoing studies are concerned with regulation of the expression of collagen genes as well as the collagen-specific enzymes prolyl hydroxylase and lysyl hydroxylase, especially with respect to ascorbic acid, an inducer of collagen synthesis, and minoxidil, a drug that we have recently found to specifically inhibit the synthesis of lysyl hydroxylase. We propose studies designed to understand the mechanism of these effects at the molecular level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR028304-10
Application #
3155635
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1981-04-01
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Yeowell, H N; Marshall, M K; Walker, L C et al. (1994) Regulation of lysyl oxidase mRNA in dermal fibroblasts from normal donors and patients with inherited connective tissue disorders. Arch Biochem Biophys 308:299-305
Murad, S; Walker, L C; Tajima, S et al. (1994) Minimum structural requirements for minoxidil inhibition of lysyl hydroxylase in cultured fibroblasts. Arch Biochem Biophys 308:42-7
Phillips, C L; Combs, S B; Pinnell, S R (1994) Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts. J Invest Dermatol 103:228-32
Handa, J T; Murad, S; Jaffe, G J (1993) Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity. Invest Ophthalmol Vis Sci 34:567-75
Halperin, E C; Gaspar, L; George, S et al. (1993) A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. CNS Cancer Consortium. Int J Radiat Oncol Biol Phys 26:413-6
Phillips, C L; Tajima, S; Pinnell, S R (1992) Ascorbic acid and transforming growth factor-beta 1 increase collagen biosynthesis via different mechanisms: coordinate regulation of pro alpha 1(I) and Pro alpha 1(III) collagens. Arch Biochem Biophys 295:397-403
Murad, S; Tennant, M C; Pinnell, S R (1992) Structure-activity relationship of minoxidil analogs as inhibitors of lysyl hydroxylase in cultured fibroblasts. Arch Biochem Biophys 292:234-8
Darr, D; Combs, S; Dunston, S et al. (1992) Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage. Br J Dermatol 127:247-53
Yeowell, H N; Ha, V; Walker, L C et al. (1992) Characterization of a partial cDNA for lysyl hydroxylase from human skin fibroblasts;lysyl hydroxylase mRNAs are regulated differently by minoxidil derivatives and hydralazine. J Invest Dermatol 99:864-9
Phillips, C L; Lever, L W; Pinnell, S R et al. (1991) Construction of a full-length murine pro alpha 2(I) collagen cDNA by the polymerase chain reaction. J Invest Dermatol 97:980-4

Showing the most recent 10 out of 12 publications