Modeling How Epidermal Homeostasis is Achieved

Abstract

Homeostasis in skin epidermis, the first line of defense against potential damage due to environmental exposures and external stress, is the key element of epithelial tissue maintenance. It is known that cell proliferation in the basal layer of skin epidermis is balanced with cell loss of terminally differentiated cells in the outermost surface. It is fundamentally important to understand the dynamic characteristics of the epidermal homeostasis, because understanding the epidermal homeostasis is the first step toward unraveling the mechanisms on skin diseases and cancer. In this work, we develop a computational model to investigate how skin epidermal homeostasis is achieved through cell proliferation, differentiation, and cell loss. As a recent study showed, cell division, as well as cell loss events, is described as stochastic in our model. Important factors such as cell size changes during the differentiation are included in the model. Our results reveal that coupling effects are crucial in maintaining skin epidermal structure. In particular, coupling effects both on cell division and cell loss are required to maintain the epidermis. Our model also predicts that mechano-biological coupling in basal progenitor cell division has a dominant role in the epidermal homeostasis, as shown in a recent study where, upon disruption of cell-cell junctions in skin tissue, proliferation and apoptotic rates of epithelial cells are dramatically changed, leading to possible disease states. Strong coupling effect on cell division leads to stable epidermal structure with wider ranges of other parameters including cell loss rate and coupling parameters in this study. Our model also predicts aberrant situations that mimic skin diseases such as palmoplantar keratodermas (PPK) by varying model parameters, which in turn confirms the existence and importance of coupling effects. Hence consideration of mechano-biological coupling in the tissue would also have high clinical relevance.