¹Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, California, USA

Correspondence: Dr Fu-Tong Liu, Department of Dermatology, University of California, Davis, School of Medicine, 3301 C Street, Suite 1400, Sacramento, California 95816, USA. E-mail: fliu@ucdavis.edu

Received 30 November 2007; Revised 16 March 2008; Accepted 18 March 2008; Published online 8 May 2008.

Abstract

Keratinocytes undergo apoptosis in a variety of physiological and pathological conditions. Galectin-3 is a member of a family of -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.