Osteopontin promotes keratinocyte proliferation by G0/G1 cell cycle arrest in psoriasis

Psoriasis is a chronic inflammatory dermatological disorder that is featured by the abnormal activation of epidermal keratinocytes. Osteopontin (OPN) is a multifunctional phosphoprotein upregulated in psoriasis. OPN levels in the skin of psoriasis patients and healthy subjects were assessed by immunohistochemistry. To evaluate the potential role of OPN in keratinocyte proliferation, the knockdown model of OPN was constructed using OPN siRNA. The proliferative activity of HaCaT cells was assessed via the CCK-8 and EdU cell proliferation assays. The cell cycle and Apoptosis were analyzed using flow cytometry. Western blot assay was conducted in order to investigate the expression levels of cyclins, CDKs, and apoptosis-associated proteins. OPN expression was increased in the epidermis of psoriasis lesions and OPN knockdown inhibited the proliferation of keratinocytes. OPN affected keratinocyte proliferation by G0/G1 cell cycle arrest and promoted their Apoptosis, which involved the regulation of cyclins (Cyclin D1 and Cyclin A2), cyclin-dependent kinases (CDK2 and CDK4), and Apoptosis proteins (Bim, Bcl-2, and Caspase-3) in keratinocytes. OPN expression was significantly higher in keratinocytes of psoriasis lesions. OPN knockdown inhibited the keratinocyte proliferation, arrested the G0/G1 cell cycle, and promoted Apoptosis. This suggests that OPN may provide a new mechanism for the proliferation of keratinocytes in psoriasis.

Apoptosis; Cell cycle; Keratinocytes; Osteopontin; Proliferation.