title: Galectin-7 Regulates Keratinocyte Proliferation and Differentiation through JNK-miR-203-p63 Signaling.
abstract: Galectin-7, a member of the β-galactoside-binding protein family, is primarily expressed in stratified epithelial cells, including keratinocytes. There is information in the literature suggesting a role for this protein in regulation of keratinocyte survival and growth, but the underlying mechanism remains relatively unknown. Moreover, its expression pattern in the epidermis suggests that it is also involved in the regulation of keratinocyte differentiation. Here, we demonstrate that galectin-7 knockdown results in reduced differentiation and increased proliferation of keratinocytes. Using microarray and deep-sequencing analyses, we found that galectin-7 positively and negatively regulates microRNA (miR)-203 and miR-146a expression, respectively. We show that galectin-7 regulates keratinocyte differentiation and proliferation through miR-203 but not miR-146a. A knockdown of either galectin-7 or miR-203 in keratinocytes increases expression of p63, an essential transcription factor involved in skin development. Rescue of miR-203 expression in a galectin-7 knockdown model reduces p63 expression to baseline. Increased galectin-7 expression upregulates c-Jun N-terminal kinase (JNK) protein levels, which is required for miR-203 expression. Finally, we establish that galectin-7 can be associated with JNK1 and protect it from ubiquitination and degradation. Thus, our data suggest an intracellular function of galectin-7: regulation of keratinocyte proliferation and differentiation through the JNK1-miR-203-p63 pathway.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Hung-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chiang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lo
authors.affiliation: Graduate institute of immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuan-Hsin
authors.initials: YH
authors.lastname: Lo
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hsu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Huan-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Graduate institute of immunology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, California, USA. Electronic address: ftliu@ibms.sinica.edu.tw.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D037161:Galectins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015603:Keratinocytes / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D037161:Galectins; C092525:LGALS7 protein, human; D035683:MicroRNAs