Abstract
Keratinocytes undergo apoptosis in a variety of physiological and pathological conditions. Galectin-3 is a member of a family of beta-galactoside-binding animal lectins expressed abundantly in keratinocytes and other epithelial cells. Here, we have studied the regulatory role of galectin-3 in keratinocyte apoptosis by using cells from gene-targeted galectin-3 null (gal3(-/-)) mice. We showed that galectin-3 mRNA was transiently upregulated in ultraviolet-B (UVB)-irradiated wild-type keratinocytes. We found that gal3(-/-) keratinocytes were significantly more sensitive to apoptosis induced by UVB as well as various other stimuli, both in vitro and in vivo, than wild-type cells. Moreover, we demonstrated that increased apoptosis in gal3(-/-) keratinocytes was attributable to higher extracellular signal-regulated kinase (ERK) activation and lower AKT activation after UVB irradiation. We conclude that endogenous galectin-3 is an anti-apoptotic molecule in keratinocytes functioning by suppressing ERK activation and enhancing AKT activation and may play a role in the development of apoptosis-related skin diseases.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / radiation effects*
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Dermatitis, Allergic Contact / metabolism
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Dermatitis, Allergic Contact / pathology
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Dermatitis, Allergic Contact / physiopathology
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Enzyme Activation / radiation effects
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Etoposide / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Galectin 3 / deficiency
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Galectin 3 / genetics
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Galectin 3 / metabolism*
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Galectins / metabolism
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Hydrogen Peroxide / pharmacology
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JNK Mitogen-Activated Protein Kinases / metabolism
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Keratinocytes / drug effects
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Keratinocytes / metabolism
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Keratinocytes / physiology*
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Keratinocytes / radiation effects
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Oxidants / pharmacology
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Phosphorylation / radiation effects
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA, Messenger / metabolism
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Skin / cytology
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Skin / radiation effects
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Ultraviolet Rays / adverse effects*
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Up-Regulation
Substances
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Galectin 3
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Galectins
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Oxidants
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Protein Kinase Inhibitors
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RNA, Messenger
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Etoposide
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Hydrogen Peroxide
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases