Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation.
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.
Saegusa
Jun
J
Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California 95816, USA.
Hsu
Daniel K
DK
Liu
Wei
W
Kuwabara
Ichiro
I
Kuwabara
Yasuko
Y
Yu
Lan
L
Liu
Fu-Tong
FT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D017449:Dermatitis, Allergic Contact / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation / Q000528:radiation effects; D005047:Etoposide / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation / Q000528:radiation effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation
D037502:Galectin 3; D037161:Galectins; D016877:Oxidants; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D005047:Etoposide; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases