BAG-1L promotes keratinocyte differentiation in organotypic culture models and changes in relative BAG-1 isoform abundance may lead to defective stratification

CAM Hinitt, TM Benn, S Threadgold, J Wood, AC Williams, A Hague

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)

Abstract

In keratinocytes the human Bag-1 gene produces three different protein isoforms from a single messenger RNA, BAG-1L, BAG-1M and BAG-1S. In this study we questioned whether BAG-1L or the shorter isoforms would promote keratinocyte differentiation in organotypic cultures of HaCaT. HaCaT parental and vector cells showed stratification, but terminal differentiation was not complete. Cultures overexpressing BAG-1L isoform-specifically were of increased thickness, demonstrated pronounced expression of basal cytokeratin 5 and β1-integrin, suprabasal involucrin, cytokeratin 1 and plasma membrane-localised filaggrin, and a marked keratinized layer of cells at the surface. We were unable to overexpress BAG-1S and BAG-1M isoform-specifically. Overexpression of BAG-1M gave rise to organotypic cultures intermediate in differentiation to controls and those overexpressing BAG-1L. Cells overexpressing BAG-1S also exhibited elevated endogenous BAG-1. These produced slow growing cultures with high levels of basal cytokeratin 5, but little involucrin or cytokeratin 1. Suprabasal β1-integrin and Ki67 positive cells indicated defective stratification. The results suggest that BAG-1L potentiates epidermal differentiation, but disruption in the relative balance of isoforms towards overexpression of BAG-1S can lead to defective tissue patterning. Hence, a delicate balance of BAG-1 isoforms may be required to regulate normal epidermal stratification and differentiation, with important implications for aberrant differentiation in cancer.
Translated title of the contributionBAG-1L promotes keratinocyte differentiation in organotypic culture models and changes in relative BAG-1 isoform abundance may lead to defective stratification
Original languageEnglish
Pages (from-to)2159 - 2170
Number of pages11
JournalExperimental Cell Research
Volume317
Issue number15
DOIs
Publication statusPublished - 10 Sep 2011

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