Phospholipase C gamma 1 is required for normal irritant contact dermatitis responses and sebaceous gland homeostasis

Abstract

Differentiation and proliferation of keratinocyte are controlled by various signalling pathways. The epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Inhibition of EGFR signalling disturbs keratinocyte proliferation, differentiation and migration. Previous studies have revealed that one of the EGFR downstream signalling molecules, phospholipase C gamma 1 (PLC gamma 1), regulates differentiation, proliferation and migration of keratinocytes in in vitro cell culture system. However, the role of PLC gamma 1 in the regulation of keratinocyte functions in animal epidermis remains unexplored. In this study, we generated keratinocyte-specific PLC gamma 1 knockout (KO) mice (PLC gamma 1 cKO mice). Contrary to our expectations, loss of PLC gamma 1 did not affect differentiation, proliferation and migration of interfollicular keratinocytes. We further examined the role of PLC gamma 1 in irritant contact dermatitis (ICD), in which epidermal cells play a pivotal role. Upon irritant stimulation, PLC gamma 1 cKO mice showed exaggerated ICD responses. Further study revealed that epidermal loss of PLC gamma 1 induced sebaceous gland hyperplasia, indicating that PLC gamma 1 regulates homeostasis of one of the epidermal appendages. Taken together, our results indicate that, although PLC gamma 1 is dispensable in interfollicular keratinocyte for normal differentiation, proliferation and migration, it is required for normal ICD responses. Our results also indicate that PLC gamma 1 regulates homeostasis of sebaceous glands.