Pattern of expression of CCN family members Cyr61, CTGF and NOV in human acute and chronic wounds

Abstract

Abstract. The CCN family is a group of extremely cysteinerich proteins that are found within the extracellular matrix and are comprised of cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN 2) and nephroblastoma overexpressed (NOV/CCN3). Collectively, these proteins stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration, and regulate angiogenesis, tumour growth, placentation, implantation, embryogenesis and endochondral ossification. Despite such diverse activity, CCN protein function has not been explored in human wounds and healing. In the present study, we investigated the expression of these proteins in samples of normal, acute and chronic wounds using immunohistochemical staining and real-time quantitative RT-PCR. Statistical analysis was performed using the Fisher's exact test. Our results showed that, although all CCN proteins were present in normal, acute and chronic wounds, their expression levels differed, particularly in the case of connective tissue growth factor (CTGF), for which significantly reduced levels were found in chronic wounds compared to acute wounds (p<0.002). Thus, the lack of CTGF in wound tissues may contribute to the abnormal healing of clinical wounds. This suggests that CCN proteins may play an important role in human tissue wound healing. This further suggests that human wound healing may be promoted by manipulating the levels of this protein.

Matrix protein CCN1 induced by bacterial DNA and CpG ODN limits lung inflammation and contributes to innate immune homeostasis

“… 20 In another example, CCN1 has been reported previously to promote inflammation and wound repair. 38 - 40 In these studies, Bai et al demonstrated that a high dose of CCN1 (10 μg/ml) treatment leads to an up-regulation of pro-inflammatory cytokine/chemokine mRNAs in macrophages. 38 CCN1 supports the adhesion of macrophages, activates NF-κB mediated transcription, and induces pro-inflammatory cytokines which are generated by classically activated M1 macrophages.…”

CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis

“…The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family comprises six highly conserved cysteine rich proteins. Mounting evidence suggests the critical roles of CCN family in various cell processes including proliferation and adhesion, homeostasis, osteoblast differentiation, wound repair, inflammation, fibrosis and tumorigenesis ( 7 – 9 ). Of these members, connective tissue growth factor (CTGF)/CCN2 acts as an ECM protein and is associated with wound healing and scar formation ( 10 , 11 ).…”

Integrins in Wound Healing

“…142 In chronic human wounds, the expression of CCN1/Cyr61 is increased, and CCN2/CTGF is significantly reduced compared with normally healing wounds. 149 The excessive expression of CCN1/ Cyr61 may result in premature a 6 b 1 -integrinmediated myofibroblast senescence that is associated with early down-regulation of ECM (e.g., collagen) production, up-regulation of matrix-degrading proteases, and ongoing breakdown of the granulation tissue before the re-epithelialization is completed, contributing to the wound chronicity. 142,146 In hypertrophic scars, myofibroblasts persist and 778 they continue to produce excessive matrix possibly because of a reversed CCN1/ Cyr61 and CCN2/CTGF balance.…”