Activation of kinin B(1) receptor triggers differentiation of cultured human keratinocytes
Background: Keratinocyte life span is modulated by receptors that control proliferation and differentiation, key processes during cutaneous tissue repair. The kinin B1 receptor (B1R) has been reported in normal and pathological human skin, but so far there is no information about its role in keratinocyte biology. Objectives: To determine the consequence of kinin B1R stimulation on tyrosine phosphorylation, a key signalling mechanism involved in keratinocyte proliferation and differentiation. Methods: Subconfluent primary cultures of human keratinocytes were used to investigate tyrosine phosphorylation, epidermal growth factor receptor (EGFR) transactivation, cell proliferation and keratinocyte differentiation. Cell proliferation was assessed by measuring bromodeoxyuridine incorporation whereas assessment of cell differentiation was based on the expression of filaggrin, cytokeratin 10 (CK10) and involucrin. Results: The major proteins phosphorylated, after B1R stimulation, were of molecular mass 170, 125, 89 and 70 kDa. The 170- and 125-kDa proteins were identified as EGFR and p125FAK, respectively. Phosphorylation was greatly reduced by GF109203X and by overexposure of keratinocytes to phorbol 12-myristate 13-acetate, indicating the participation of protein kinase C. B1R stimulation did not increase [Ca2+]i, but triggered EGFR transactivation, an event that involved phosphorylation of Tyr845, Tyr992 and Tyr1068 of EGFR. B1R stimulation did not elicit keratinocyte proliferation, but triggered cell differentiation, visualized as an increase of filaggrin, CK10 and involucrin. Blockade of EGFR tyrosine kinase by AG1478, before B1R stimulation, produced an additional increase in filaggrin expression. Conclusions: The kinin B 1R may contribute to keratinocyte differentiation and migration by triggering specific tyrosine signalling pathways or by interacting with the ErbB receptor family. Â© 2008 The Authors.
|Título según WOS:||Activation of kinin B(1) receptor triggers differentiation of cultured human keratinocytes|
|Título según SCOPUS:||Activation of kinin B1 receptor triggers differentiation of cultured human keratinocytes|
|Título de la Revista:||BRITISH JOURNAL OF DERMATOLOGY|
|Fecha de publicación:||2008|
|Página de inicio:||792|