Abstract
BackgroundThe human epidermis is comprised of several layers of specialized epithelial cells called keratinocytes. Normal homoeostasis of the epidermis requires that the balance between keratinocyte proliferation and terminal differentiation be tightly regulated. The mammalian serine/threonine kinases (ROCK1 and ROCK2) are well-characterised downstream effectors of the small GTPase RhoA. We have previously demonstrated that the RhoA/ROCK signalling pathway plays an important role in regulation of human keratinocyte proliferation and terminal differentiation. In this paper we addressed the question of which ROCK isoform was involved in regulation of keratinocyte differentiation.Methodology and Principal FindingsWe used RNAi to specifically knockdown ROCK1 or ROCK2 expression in cultured human keratinocytes. ROCK1 depletion results in decreased keratinocyte adhesion to fibronectin and an increase in terminal differentiation. Conversely, ROCK2 depletion results in increased keratinocyte adhesion to fibronectin and inhibits terminal differentiation.ConclusionThese data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation.
Highlights
The human epidermis is comprised of several layers of specialized epithelial cells called keratinocytes
These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation
As keratinocytes are lost from the outermost epidermal layers, they are replaced through a process of terminal differentiation in which keratinocytes in the basal layer exit the cell cycle, down-regulate adhesion to the extracellular matrix (ECM) proteins of the basal lamina and migrate upwards through the supra-basal, differentiated layers, until they eventually reach the outermost cornified layer [1]
Summary
The human epidermis is comprised of several layers of specialized epithelial cells called keratinocytes. Keratinocytes in the basal layer of the epidermis adhere to these ECM proteins via integrin adhesion receptors and there is considerable evidence that adhesion to ECM plays a key role in regulating epidermal function [1]. Normal epidermal function requires that the balance between keratinocyte proliferation, adhesion to ECM proteins and terminal differentiation be tightly regulated. RhoA is a member of the Rho family of small GTPases and acts as a molecular switch to regulate a plethora of cellular processes including organisation of the actin cytoskeleton, cell adhesion and motility and gene expression [7]. Normal homoeostasis of the epidermis requires that the balance between keratinocyte proliferation and terminal differentiation be tightly regulated. We have previously demonstrated that the RhoA/ROCK signalling pathway plays an important role in regulation of human keratinocyte proliferation and terminal differentiation. In this paper we addressed the question of which ROCK isoform was involved in regulation of keratinocyte differentiation
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