Concentrations of MMP-9 and TIMP-1 in lip tissue and their impact on cleft lip surgery healing

Abstract

Aim. To compare aspects of wound healing after cleft lip surgery performed within one week of age and wound healing after surgery performed within 2 -4 months of age, especially concentrations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in tissue removed during surgery. Methods. 34 tissue samples (26 boys and 8 girls) were removed during surgery within one week of age (n=19) or within 2 -4 months of age (n=15). Tissue samples were separated into epidermis, dermis and mucous membrane. Proteins were extracted in cacodylic buffer for 24 h at a temperature 2 -8 ºC. Total protein concentrations were examined using a modification of the Lowry method. Samples were examined using ELISA kit Amersham Biotrak Activity Assay (GE Healthcare UK) for detection of MMP-9 and TIMP-1 concentrations. Results. MMP-9: early surgery -epidermis 2.168±3.303 μg/g of protein (mean±SD), dermis 1.251±1.848 µg/g, 2 -4 months surgery -epidermis 0.347±0.212 μg/g, dermis 0.555±0.276 µg/g. TIMP-1: early surgery -epidermis 1.762±2.162 μg/g, dermis 1.628±0.822 µg/g, mucous membrane 2.066±1.717 µg/g, 2 -4 months surgery -epidermis 1.881±2.810 μg/g, dermis 3.117±1.540 µg/g, mucous membrane 4.833±6.550 µg/g. Conclusions.There were no significant differences in concentrations of protein MMP-9 in epidermis and dermis and TIMP-1 in epidermis and mucous membrane according to time of surgery. Significantly decreased levels of TIMP-1 in dermis were found in samples obtained from early surgery compared to levels in samples obtained from 2 -4 months surgery.

Characteristics of Neuropeptide-Containing Innervation, Tissue Remodeling, Growth, and Vascularity in Noses of Patients With Cleft Lip and Palate

“…Our obtained values of an increased number of MMP2-and MMP-9-positive cells correlate favorably with IMH studies (Smane-Filipova et al, 2016). Notably, the surgical manipulations do not interfere with MMP9 expression in the lip tissue after surgery; thus, we may conclude that the tissue is not affected by previous repair procedures (Blaha et al, 2013). Therefore, we suggest that the increased number of MMPs-positive structures in our study shows an active degradation process in CLP.…”

siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I

“…Among their many functions are important roles in both wound healing and tissue remodeling. TIMP-1 levels of dermis early after surgery are lower than in those collected 2-4 months later (Blaha et al, 2012). Moreover, relative levels of MMP-9 and TIMP-1 as well as MMP-9/TIMP-1 protein ratios are decreased in diabetic mice (Bermudez et al, 2011).…”

Functional Morphology of Tissues in Ontogenetic Aspect in Children with Complete Bilateral Cleft Lip and Palate. Summary of the Doctoral Thesis

“…In our study, which was carried out with unilateral and bilateral cleft-affected tissues postnatally, we found a marked MMP-9 expression in milder cleft cases, but in more severe cases, i.e., in patients with complete bilateral cleft lip and palate, we found a significantly reduced MMP-9 presence. The same results have been acquired by Czech scientists with tissues from cheiloplasty in children from two to four months (Blaha et al, 2013). In the experiments with animals it was found, that increased MMP-9 activity points to hypertrophic scarring during the wound healing, and an excessive collagen production in contrast to its decreased degradation (Hosokawa et al, 2003;Manuel and Gawronska-Kozak, 2006).…”