Differential effects of Wnt5a on the proliferation, differentiation and inflammatory response of keratinocytes

The predominant role of Wnt family member 5A (Wnt5a) is to induce non-canonical Wnt signalling pathways, including the Wnt-Ca2+ and Wnt-planar cell polarity pathways. Enhanced Wnt5a expression is involved in the formation of psoriatic plaques; however, its mechanistic role remains to be determined. In the present study, the effects of Wnt5a expression on HaCaT keratinocytes were investigated. HaCaT cells were cultured in medium supplemented with 0, 40 or 80 ng/ml Wnt5a for 24 h. Cell proliferation, the cell cycle, gene expression and inflammatory responses were investigated using Cell-Counting Kit-8 assays, flow cytometry analyses, reverse transcription-quantitative polymerase chain reaction analyses and enzyme-linked immunosorbent assays, respectively. Wnt5a treatment was revealed to suppress cell proliferation in HaCaT cells. Furthermore, Wnt5a was also demonstrated to increase the proportion of HaCaT cells arrested at the G2/M phase of the cell cycle, but reduce the proportion of HaCaT cells arrested at G0/G1 phase cells. In addition, the expression levels of the differentiation markers, including filaggrin, keratin 1 and keratin 10 were revealed to be downregulated in HaCaT cells. Expression of the canonical Wnt signalling genes (-catenin and cyclin D1) and proliferation markers, such as Ki-67 and proliferating cell nuclear antigen in HaCaT cells were also revealed to be downregulated. However, the expression levels of inflammatory response markers (interferon-, interleukin-8 and interleukin-17A) were revealed to be upregulated in HaCaT cells following Wnt5a treatment. These findings suggest that Wnt5a expression may be involved in the inhibition of cell differentiation and the induction of an inflammatory response in patients with psoriasis.