Divergent regulation of proteoglycan and glycosaminoglycan free chain expression in human keratinocytes and melanocytes |
| |
Authors: | Michael Piepkorn Peter Hovingh Alexa Dillberger Alfred Linker |
| |
Institution: | (1) Department of Medicine (Dermatology), University of Washington School of Medicine, 98195 Seattle, Washington;(2) Department of Pathology, University of Washington School of Medicine, 98195 Seattle, Washington;(3) Departments of Pathology and Biochemistry, University of Utah School of Medicine and the Veterans Affairs Medical Center, 84148 Salt Lake City, Utah;(4) Clonetics Corporation, 92123 San Diego, California |
| |
Abstract: | Summary Keratinocytes and melanocytes, which together form units of structure and function within human epidermis, are known to differ
in expression of autocrine growth factors, particularly those with heparin binding affinity. Because such cytokines could
be regulated by the endogenous heparinlike glycosaminoglycan, heparan sulfate, proteoglycan synthesis was compared between
human keratinocytes and melanocytes cultured from a common donor. Following steady-state isotopic labeling under conditions
of active growth (low density cultures) and growth inhibition (high density cultures), the sulfated polymers were isolated
from conditioned media and cell extracts. We found that keratinocytes produced substantially more sulfated glycosaminoglycans
than did the melanocytes. There was no evidence for hyaluronic acid synthesis by the melanocytes. The majority of 35S]-sulfate labeling was in the heparan sulfates of the keratinocytes and in the chondroitin sulfates of the melanocytes. During
the transition from active growth to growth inhibition, there was increased heparan sulfate proteoglycan and free chain synthesis
by keratinocytes but not by melanocytes, and chondroitin sulfate proteoglycan production declined in both cell lineages. The
differences may reflect divergent evolution as each cell type came to exploit those complex polysaccharides in different ways
to regulate molecular pathways of growth and differentiation. The coupling of growth inhibition with augmented synthesis of
heparan sulfates observed for the keratinocytes suggests a regulatory role in growth factor signaling in that cell type. |
| |
Keywords: | keratinocyte melanocyte heparan sulfate proteoglycan glycosaminoglycan carbohydrate |
本文献已被 SpringerLink 等数据库收录! |
|