Par3 regulates the asymmetric division of basal stem cells in psoriasis via the Par3/mInsc/LGN signaling axis

Abstract

ObjectiveThis research aimed to investigate the mechanism in psoriasis with the involvement of Par3-containing exosomes from macrophages by regulating the asymmetric division of basal stem cells. MethodsBrdU labeling and double immunofluorescence assays were conducted to detect the proportion of asymmetric division in psoriasis mice. Western blot assay was conducted to examine the expression of Par3/mInsc/LGN signaling pathway-related proteins in psoriasis mice. Next, the asymmetric division of keratinocytes in normal mice treated with macrophages and their secreted exosomes were determined, together with the related protein detection. After establishing a macrophage-specific Par3 knockout mouse model, the asymmetric division of isolated keratinocytes and the related proteins were measured. An epidermal-specific mInsc, LGN, or NuMA knockout mouse model was induced, followed by the determination of the asymmetric division of isolated keratinocytes. ResultsThe asymmetric division of basal stem cells was increased, and the expression of Par3/mInsc/LGN signaling pathway-related proteins was elevated in psoriasis. Par3-containing macrophage-derived exosomes enhanced asymmetric division of basal stem cells and expression of Par3/mInsc/LGN signaling pathway-related proteins in mice. However, mice with Par3 loss presented opposite trends. There was a decreased asymmetric division of basal stem cells in epidermal-specific mInsc, LGN, and NUMA knockout mice. ConclusionOur study suggests that macrophage-derived exosomes-shuttled Par3 are absorbed by the basal stem cells and regulate the asymmetric division of cells to produce a large number of transit-amplifying cells, thus causing psoriasis-related symptoms in conjunction with various other factors.