Protein Kinase CK2 Promotes Proliferation, Abnormal Differentiation, and Proinflammatory Cytokine Production of Keratinocytes via Regulation of STAT3 and Akt Pathways in Psoriasis.
Wenjie HuangXuyu ZhengQi HuangDanlin WengShifei YaoCui ZhouQian LiYulian HuWenchun XuKun HuangPublished in: The American journal of pathology (2023)
Protein kinase CK2 is a constitutively active and ubiquitously expressed serine/threonine kinase that is closely associated with various types of cancers, autoimmune disorders, and inflammation. However, the role of CK2 in psoriasis remains unknown. Herein, the study indicated elevated expression of CK2 in skin lesions from patients with psoriasis and from psoriasis-like mice. In the psoriasis-like mouse model, the CK2-specific inhibitor CX-4945 ameliorated imiquimod-induced psoriasis symptoms with reduced proliferation, abnormal differentiation, inflammatory cytokine production (especially IL-17A) of keratinocytes, and infiltration of γδ T cells. In in vitro studies, exogenous CK2 promoted hyperproliferation and abnormal differentiation of human keratinocytes, which were reversed by the suppression of CK2 with CX-4945 or siRNA. Furthermore, knockdown of CK2 reduced IL-17A expression and abolished IL-17A-induced proliferation and inflammatory cytokine expression in keratinocytes. Interestingly, IL-17A increased the expression of CK2 in keratinocytes, thereby establishing a positive feedback loop. In addition, suppression of CK2 inhibited the activation of STAT3 and Akt signaling pathways in human keratinocytes and imiquimod-induced psoriatic lesions of mice. These findings indicate that a highly expressed CK2 level in the skin lesions is required in the development of psoriasis by promoting epidermal hyperplasia, abnormal differentiation, and inflammatory response via regulation of the STAT3 and Akt signaling pathways. CK2 may be a target for the treatment of psoriasis.
Keyphrases
- protein kinase
- signaling pathway
- poor prognosis
- cell proliferation
- wound healing
- endothelial cells
- mouse model
- high glucose
- inflammatory response
- oxidative stress
- induced apoptosis
- transcription factor
- long non coding rna
- physical activity
- drug induced
- systemic lupus erythematosus
- drug delivery
- atopic dermatitis
- depressive symptoms
- insulin resistance
- endoplasmic reticulum stress
- epithelial mesenchymal transition
- lipopolysaccharide induced
- disease activity
- induced pluripotent stem cells
- young adults