Blimp-1 induction by EGF involves in regulation of keratinocyte differentiation, migration and inflammation

抄録

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor, and plays a crucial role in the regulation of development and functions of various immune cells. Currently, there is limited understanding about the regulation of Blimp-1 expression and the crosstalk between EGFR and Blimp-1 in skin homeostasis. In this study, we investigated the regulation and functional link between EGFR and Blimp-1 in human epidermal keratinocytes. We found that EGFR activation by EGF and TGF-alpha could upregulate the protein and mRNA levels of Blimp-1 in human primary and HaCaT keratinocytes. This effect was dependent on PKC, p38, and ERK activation, but not STATs signaling induced by EGFR. Additionally, the stability of Blimp-1 protein was under the control of the proteasome and lysosome degradation systems, and EGF could also upregulate Blimp-1 expression in human skin squamous cell carcinomas. Moreover, Blimp-1 knockdown enhanced the EGFR-mediated IL-8, CXCL5 and IL-6 gene expression and keratinocyte migration, but reduced the EGFR-mediated suppression of differentiation marker keratin 10. Confluence-induced keratinocyte expression of K10 was enhanced, but loricrin expression was reduced in Blimp-1 silencing keratinocytes. In conclusion, our findings shed new insights into the regulation and functional role of Blimp-1 to timely balance the inflammation, differentiation, and migration of keratinocytes under constitutive EGFR activation.