As the major constituent cells of a renewing epidermis, keratinocytes are programmed to differentiate as they progress from the basal layer to the stratum corneum. In vitro, many of the changes characteristic of the differentiated phenotype can be induced by raising the extracellular Ca+2. This project is designed to examine whether membrane currents play a role in keratinocyte differentiation. Membrane currents of proliferative and differentiated keratinocytes will be defined and compared. Keratinocytes will be studied with a dual approach, correlating membrane currents with markers of differentiation. Agents which modify membrane currents will be tested for their ability to affect differentiation of cultured keratinocytes. This research may produce insight into the in vivo process of keratinocyte differentiation. Agents which modulate membrane currents and influence in vitro differentiation of cultured keratinocytes could be used to modulate growth and differentiation of keratinocytes in vivo. Information derived from this project could be applied to clinical problems such as wound healing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR001853-06
Application #
2077329
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1991-01-15
Project End
1995-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Dermatology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Mauro, T; Holleran, W M; Grayson, S et al. (1998) Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res 290:215-22
Mauro, T; Dixon, D B; Komuves, L et al. (1997) Keratinocyte K+ channels mediate Ca2+-induced differentiation. J Invest Dermatol 108:864-70
Grando, S A; Horton, R M; Mauro, T M et al. (1996) Activation of keratinocyte nicotinic cholinergic receptors stimulates calcium influx and enhances cell differentiation. J Invest Dermatol 107:412-8
Mauro, T; Dixon, D B; Hanley, K et al. (1995) Amiloride blocks a keratinocyte nonspecific cation channel and inhibits Ca(++)-induced keratinocyte differentiation. J Invest Dermatol 105:203-8
Lee, S H; Elias, P M; Feingold, K R et al. (1994) A role for ions in barrier recovery after acute perturbation. J Invest Dermatol 102:976-9
Mauro, T M; Isseroff, R R; Lasarow, R et al. (1993) Ion channels are linked to differentiation in keratinocytes. J Membr Biol 132:201-9