Combined treatment with sodium butyrate and PD153035 enhances keratinocyte differentiation.
Epidermal growth factor (EGF) receptor (EGFR) signalling is a critical determinant of keratinocyte proliferation and differentiation in both normal and diseased skin. Here we explore the effects of combined treatment with the differentiation-promoting agent sodium butyrate (SB) and the EGFR inhibitor (EGFRI) PD153035 on terminal differentiation of normal human epidermal keratinocytes (NHEKs). Cells treated with SB showed increased expression of the levels of mRNA and protein of the differentiation markers filaggrin and transglutaminase 1. Cotreatment with EGF significantly blunted these effects of SB. Combined treatment with SB and PD153035 alleviated these inhibitory actions of EGF, resulting in improved effects of decreased cell growth and increased terminal differentiation, relative to the individual treatments. These results indicate that the combined use of a differentiation-promoting agent and an EGFR inhibitor may offer an additional approach to the management of hyperproliferative skin diseases.
Department of Biological Sciences, University of Memphis, Memphis, TN, USA.
Sandra
S
Leon Carrion
Carrie Hayes
CH
Sutter
Thomas R
TR
Sutter
D000970:Antineoplastic Agents / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000091344:Filaggrin Proteins; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006633:Histamine Antagonists; D007381:Intermediate Filament Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D020148:Butyric Acid; D004815:Epidermal Growth Factor; D011503:Transglutaminases; C105804:transglutaminase 1; D066246:ErbB Receptors; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline
differentiation; epidermal growth factor receptor; keratinocyte; psoriasis; sodium butyrate