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

Abstract

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 (β‑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‑γ, 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.

The Levels of Wnt5a and Its Receptors Frizzled5 and Frizzled2 as Immunohistochemical Biomarkers of Severity of Psoriasis

“… 16 In HaCaT cells, after treatment with Wnt5a, the expression levels of inflammatory markers, including IFN-γ, IL-8 and IL-17A were unregulated. 17 IL-1α, TNF-α, IFN-γ, and TGF-α can induce the expression of Wnt5a. 5 All these inflammatory markers play critical roles in the pathogenesis and maintenance of psoriasis.…”

Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity

“…Previous studies reported that several inflammatory cytokines could be upregulated, accompanied by G2/M phase arrest, by interfering with exogenous agents. 51 , 52 Therefore, we presumed that the expression of these inflammatory cytokines was elevated in the G2/M phase. Cell cycle synchronization of ccRCC cells was performed, and we detected their expression patterns in different phases.…”

The pathological role of Wnt5a in psoriasis and psoriatic arthritis

“…Subsequently, autocrine Wnt5a promotes the differentiation of NHEKs . In contrast, Wnt5a treatment can suppress HaCaT keratinocyte proliferation and differentiation, although the expression of IL‐8, IL‐17A and interferon‐γ was up‐regulated . It is difficult to interpret these somewhat contradictory results, but they indicate a complex and as yet unclear role of Wnt5a in modulating the proliferation and differentiation of keratinocytes.…”