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Alkaline Phosphatase Activity is Related to Acute Inflammation and Collagen Turnover During Acute and Chronic Wound Healing

Abstract

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. The 43 amino acid angiogenic peptide thymosin b 4 has previously been found to promote accelerated dermal wound repair in rats, aged mice and db/db diabetic mice, and corneal repair in normal rats. It has been found in great abundance in wound fluid. Here, we hypothesized that thymosin b 4 may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Western blot analysis of keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of thymosin b 4 showed changes in the expression of the MMP-1, À2, and À9. Zymographic analysis of whole excised mouse wounds taken after homogenization also showed changes in MMP-2 and-9 expression over a 3-day period. These results were confirmed in 2-day-old wounds by RT-PCR. We conclude that part of the wound healing activity of thymosin b 4 resides in its ability to increase protease activity. Since thymosin b 4 -induced protease activity can be further controlled by inflammatory cytokines, a regulatory role for thymosin b 4 is proposed in wound healing. These studies suggest that thymosin b 4 may play a pivotal role in extracellular matrix remodeling during wound repair and may be effective in the treatment of chronic wounds in humans.Fluorescence correlation spectroscopy was used to measure the binding and diffusion of growth factors in model extracellular matrices in order to investigate the importance of protein-matrix interactions in regulating signaling molecules within a three-dimensional matrix. Two important growth factors were studied, transforming growth factor b1 and basic fibroblast growth factor, which are known to have specific affinities for fibronectin and the heparansulfate-proteoglycan perlecan, respectively. Collagen-based matrices were prepared by polymerizing type I collagen in the presence of fibronectin or perlecan, and we measured diffusion constants and binding constants of the two growth factors. The binding constant measured for transforming growth factor b1 with fibronectin-containing matrices was in good agreement with that measured using affinity chromatography. However, the interactions measured between fibroblast growth factor and perlecan were significantly weaker than expected. Surprisingly, the strongest interactions by far were with monomeric collagen solutions and fibrillar collagen matrices. Our findings suggest a central role for the three-dimensional fibrillar collagen matrix in growth factor interactions, with modulatory roles for fibronectin or perlecan.

Therapeutic effect of zinc‐containing calcium phosphate suspension injection in thermal burn‐rats

“…Because plasma ALP activity is an important parameter of the healing process, it was measured in the rats with thermal burns 12. Figure 5 (left) shows that before the thermal treatment, the ALP level in the control group (group C) was around 28 IU/L, but after the treatment it fluctuated between 20 and 40 IU/L depending on the conditions.…”

“…In contrast, Kr€ otzsch et al 12 reported that the ALP activity was an acute inflammation marker because the enzyme levels were increased in acute wounds, but not in chronic inflammation processes. They concluded that the ALP activity was an important factor to be considered in acute inflammation in wound injury and their healing process in chronic wound repair.…”

“…Because plasma ALP activity is an important parameter of the healing process, it was measured in the rats with thermal burns. 12 Figure 5 (left) shows that before the thermal treatment, the ALP level in the control group (group C) was around 28 IU/L, but after the treatment it fluctuated between 20 and 40 IU/L depending on the conditions. The ALP level of group D1 and D2 rats (ZnSO 4 and a-ZnTCP ) were higher than that of the control group (group C), and showed a maximum of 48 IU/L at 4 days and 46 IU/L at 5 days, respectively.…”

Therapeutic effects of transdermal systems containing zinc-related materials on thermal burn rats

“…Krötzsch et al [17] reported that ALP activity was a marker of acute inflammation since the enzyme's levels increased in acute wounds, but not in chronic inflammation processes. They concluded that ALP activity was an important factor to be considered in acute inflammation in wound injury at the initial stage and in their healing process for chronic wound repair at the later stage.…”

Enhancement of Wound Healing in Normal and Diabetic Mice by Topical Application of Amorphous Polyphosphate. Superior Effect of a Host–Guest Composite Material Composed of Collagen (Host) and Polyphosphate (Guest)

“…In a previous contribution we could demonstrate that the expression of the fibrillar collagen genes, of types I, II, and III, are strongly upregulated in vitro by polyP microparticles, especially if they are enriched with retinol [ 21 ]. In addition, for the genes encoding for collagens, the steady-state-expression levels of aggrecan [ 22 ] (a major regulatory proteoglycan also during wound healing) and of ALP (an enzyme found in the first stage of acute wound healing) [ 23 ], increase in response to polyP [ 24 ]. These results prove the morphogenetic activity of polyP, as summarized [ 9 ] ( Figure 2 ).…”