CCN family proteins in wound healing - a pivotal role? [Abstract]

Introduction: CCN family proteins comprised of cysteine-rich 61(Cyr61/ CCN1), connective tissue growth factor (CTGF/CCN2) and nephroblastoma - overexpressed (NOV/CCN3) found in the extracellular matrix. They stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration and regulate angiogenesis. Clinically they have been shown to have a role in embryogenesis, osteochondral ossification and tumour growth, however their function has not been explored in human wound healing. Methods: Samples of normal, acute and chronic wounds were collected. Immunohistochemical staining and real time quanitative RT-PCR was performed. GAPDH was used as the house keeping control. Statistical analysis was performed using the Fisher’s exact test. Results: Immunohistochemical staining Tissue Cyr61 CTGF Nov Normal skin present-strong present-weak present-weak Acute wound unchanged decreased unchanged Chronic wound increased decreased unchanged Real time quanitative RT-PCR &Cyr61 increased in chronic wounds as compared to acute (ns). &NOV decreased in chronic wounds as compared to acute wounds (ns). & CTGF decreased in chronic wounds: CTGF/GAPDH ratio 0.017(0.0004- 0.0457); median(IQR) as compared to acute wounds 0.16 (0.00–5.42) (statistically significant; po0.002). Conclusion: CCN family members have a differential pattern of expression in normal skin and in wound tissues and therefore manipulation of these proteins may play a pivotal role in wound healing