Research Paper Volume 12, Issue 8 pp 6823—6851

Figure 8. Proposed integrated model of the intracellular and extracellular functions of IGFBP2 in psoriasis keratinocytes. In epidermal keratinocytes of psoriasis patients characterized by a pre-senescent state, IGFBP2, p21 and p16 co-localize in the nuclear compartment. Here, p21 and p16 contribute to the cell cycle arrest in phase G1, by inhibiting Cdk1/2 and Cdk4/6, respectively. The nuclear role of IGFBP2 in pre-senescent KC remains to be investigated. In senescent psoriasis KC, IGFBP2, p16 and, of note, p21 accumulate in the cytoplasm. Here, p21 is hyper-phosphorylated and inhibits apoptotic processes. In the cytoplasm, IGFBP2 physically interacts with p21 and protects it from proteasomal degradation, thus sustaining its levels, and, indirectly, contributing to the apoptosis resistance typical of affected KC. In parallel, IGFBP2 released extracellularly blocks the pro-proliferative action of IGFs by binding to it and impeding its recruitment to IGF receptor.