Cellular and molecular changes that predispose skin in chronic spinal cord injury to pressure ulcer formation

Patients with spinal cord injury have a predisposition to develop pressure ulcers. Specific characteristics of the patients' skin potentially involved have not yet been identified. The purpose of this investigation was to determine whether loss of neuronal control affects cellular and molecular homeostasis in the skin. Intact afflicted skin, wound edge of pressure ulcers, and control skin were analysed. Platelets, transforming growth factor-beta 1, and activin A were identified by immunohistochemistry. Transforming growth factor-beta-like activity was determined by bioassay, and gene expression by DNA microarray analysis or RT-PCR. In afflicted skin, enhanced platelet extravasation was detected. Transforming growth factor-beta 1 and activin A accumulated in the dermal-epidermal junction zone. Transforming growth factor-beta-like activity and activin A expression were increased in intact afflicted skin (compared to control skin) and were further enhanced in pressure ulcers. In vitro, activity was generated by fibroblast-epithelial cell interactions, which also induced activin A. Thus, loss of neuronal control in spinal cord injury appears to trigger inappropriate wound healing processes in the patients' skin. Plasma leakage and increased transforming growth factor-beta-like activity combined with shear forces potentially enhance the risk for pressure ulcer formation.