Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions

Jia,Hai-Yan; Shi,Ying; Luo,Long-Fei; Jiang,Guan; Zhou,Qiong; Xu,Shi-Zheng; Lei,Tie-Chi

doi:10.3892/ijmm.2015.2445

Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions

Authors:
- Hai-Yan Jia
- Ying Shi
- Long-Fei Luo
- Guan Jiang
- Qiong Zhou
- Shi-Zheng Xu
- Tie-Chi Lei
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Affiliations: Department of Dermatology, Wuhan University, Renmin Hospital, Wuhan, Hubei 430060, P.R. China
Published online on: December 23, 2015 https://doi.org/10.3892/ijmm.2015.2445
Pages: 359-368
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis. When we analyzed template‑DNA strand segregation in trypsin-dissociated human psoriatic keratinocytes using BrdU pulse-chase labeling, we found that the percentage of asymmetric segregation of BrdU was significantly increased in the cell pairs of psoriatic epidermal cells compared with normal epidermal cells. Furthermore, we also examined the effects of both interleukin (IL)-17A and IL-22 cytokines on the differentiation status of cultured human keratinocytes. The results indicated that both cytokines had synergistic effects on passage-one epidermal cell sheets derived from skin explants and also on cultured keratinocytes, were involved in the maintenance of the undifferentiated stem cell phenotype, and these results suggest an efficient mechanism for preventing the premature loss of basal stem-cell pools in the pro-inflammatory cytokine-enriched milieu of the psoriatic epidermis. Our findings suggest that inhibition of hyperactive stem cells represents a potential therapeutic target to combat recalcitrant epidermal hyperplasia in psoriasis.

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