Matrix Metalloproteinases In Wound Healing Research Articles

The effects of oral Aloe vera on the efficacy of transplanted human endothelial cells and the expression of matrix metalloproteinases in diabetic wound healing

BackgroundDiabetic wounds are characterized by delayed healing and impaired angiogenesis. Aloe vera and human umbilical vein endothelial cells (HUVECs) are reported to facilitate wound healing, and the former also has hypoglycemic property. Matrix metalloproteinases are enzymes that play a role in diabetic wound pathogenesis. ObjectiveTo investigate whether oral Aloe vera can enhance the efficacy of HUVEC transplantation and inhibit the expression of matrix metalloproteinases in wound healing of diabetic mice. Materials and methodsBALB/c nude mice were randomly assigned into five groups: normal control group, diabetic group (DM), DM transplanted with HUVECs, DM treated with oral Aloe vera, and DM treated with combined HUVECs and oral Aloe vera. Diabetes was induced by streptozotocin. Bilateral full-thickness excision cutaneous wounds were created. At days 7 and 14 post-wounding, the following parameters were determined: blood glucose, wound area, wound perfusion, capillary vascularity, re-epithelialization rate and tissue VEGF levels. Tissue expressions of MMP-2 and MMP-9 were compared between the DM mice and those treated with oral Aloe vera. ResultsOver days 7 and 14, Aloe vera exerted glucose-lowering effect in diabetic mice. Higher wound closure rate, blood flow and capillary vascularity, and lower MMP-2 and MMP-9 expressions were observed at both time points in DM treated with Aloe vera group compared with DM group (P < 0.05). Moreover, combined therapy of HUVECs and oral Aloe vera was more effective than Aloe vera or HUVECs alone in increasing VEGF levels, capillary vascularity and wound perfusion. Blood glucose levels were negatively correlated with angiogenesis (P = 0.000. ConclusionIt is suggested that oral Aloe vera enhances the efficacy of HUVEC transplantation on diabetic wound angiogenesis, partly through improving glycemic control. Oral Aloe vera also promotes diabetic wound healing via inhibition of MMP-2 and MMP-9 expressions.

The Role of Matrix Metalloproteinases in Wound Healing

The Role of Matrix Metalloproteinases in Wound Healing

Matrix Metalloproteinases: How Much Can They Do?

Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.

Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them.

Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.

Role of matrix metalloproteinases in wound healing after surgery of congenital cleft lip

Role of matrix metalloproteinases in wound healing after surgery of congenital cleft lip

Matrix Metalloproteinase-3 Accelerates Wound Healing following Dental Pulp Injury

Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. Angiogenesis is essential for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that certain MMPs expressed during pulp wound healing may support recovery processes. To address this issue, a rat pulp injury model was established to investigate expression of MMPs during wound healing. Real-time RT-PCR analysis showed that expression MMP-3 and MMP-9 (albeit lower extent) was up-regulated at 24 and 12 hours after pulp injury, respectively, whereas expression of MMP-2 and MMP-14 was not changed. MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. In addition, MMP-3 enhanced proliferation, migration, and survival of human umbilical vein endothelial cells in vitro. Furthermore, the topical application of MMP-3 protein on the rat-injured pulp tissue in vivo induced angiogenesis and reparative dentin formation at significantly higher levels compared with controls at 24 and 72 hours after treatment, respectively. Inhibition of endogenous MMP-3 by N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid resulted in untoward wound healing. These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and pulp wound healing.

The use of MelMax®&gt; in the healing of chronic wounds

Chronic wounds can have detrimental consequences for the quality of life of patients as well as presenting a huge financial burden to the NHS. An imbalance in the level of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) in chronic wounds impedes the healing process. In addition, high levels of bacteria in the wound bed are a common feature of chronic wounds and also cited as a major cause of delayed healing. The aim of this article is to look in more detail at the role of MMPs in wound healing as well as the antimicrobial properties of honey when combined with a dressing to combat wound infection. The article also introduces a new dressing, MelMax (distributed by CliniMed), which utilizes protease regulation and the antimicrobial properties of honey when addressing chronic wound infection. Short-term case studies are used to demonstrate how the dressing was successfully incorporated into the author's practice.

Expression of Matrix Metalloproteinases in Wound Healing after Glaucoma Filtration Surgery in Rabbits

Purpose: To investigate the protein and mRNA expressions of matrix metalloproteinases (MMPs), gelatinolytic activity and localization of MMP activity in wounds after glaucoma filtration surgery in rabbits. Methods: Sixty eyes of 30 rabbits were removed 1, 3, 7, 14 and 120 days after the surgery and used for this experiment. Protein and mRNA expressions were analyzed by immunohistochemistry and laser capture microdissection/real-time RT-PCR, respectively. The gelatinolytic activity was analyzed by gelatin zymography and the localization was studied using in situ zymography. Results: By immunohistochemistry, expression of MMP-1, MMP-2, MMP-3, MMP-9 and MT1-MMP was detected in the wounds, most markedly 3 days after the surgery. MMP-positive cells were predominantly macrophages. Expression of MMP-9 and MT1-MMP mRNAs was verified by RT-PCR. Gelatinolytic activities corresponding to proMMP-2 and the active form of MMP-2 were detected in the wounds 3 and 7 days after surgery. In situ zymography localized gelatinolytic activities at the wound site. These activities were almost completely abolished by an MMP inhibitor, indicating that the gelatinolytic activity belongs to metalloproteinases. Conclusions: MMPs, particularly MMP-2/MT1-MMP, play important roles in the degradation of the extracellular matrix in the wound healing process after glaucoma filtration surgery and may represent an important target for therapeutic intervention after glaucoma filtration surgery.

016 TNF‐alpha Mediated Induction of MMP‐9 is Modulated by P21‐activated Kinase (PAK)

Matrix metalloproteinase‐9 (MMP‐9) transiently expresses in acute wound. In non‐healed wounds, MMP‐9 together with other proteinases persistently elevate, which may lead excessive ECM degradation and failure of wound closure. To understand the molecular regulation of MMP‐9 we investigated the signal transduction for TNF‐alpha mediated induction of MMP‐9 by dermal fibroblasts. TNF‐alpha initiates three major signal pathways including NF‐11B, JUN N‐terminal kinase (JNK), and p38 MAPK. On the other hand, Rho‐GTPase plays an important role in a variety of cellular functions including cell morphogenesis, motility, survival, angiogenesis, and mitosis. It remains unknown if the “cross talk” of these signals having a role in regulation of matrix metalloproteinases (MMPs). In this study we found that over expression of the p21‐activated kinase (PAK) specifically attenuates TNF‐alpha mediated induction of MMP‐9. However, TNF‐alpha mediated induction of MMP‐3 and proMMP‐2 activation was intact. NF‐κB signal is regarded as a common pathway for many MMPs. Indeed, PAK did not affect TNF‐alpha mediated degradation of Ikappa B, suggesting additional signal is targeted by PAK. In contrast, MMP‐3 but not MMP‐9 expression is specifically blocked by p38 MAK. Thus TNF‐alpha induced expression of multiple MMPs in wound healing may utilize different intracellular signal pathways.

The role of matrix metalloproteinases in wound healing.

The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem.

Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats

Wound strength depends on the balance between collagen synthesis and degradation; however, the role of collagen breakdown in wound healing is still not well understood. We investigated the role of matrix metalloproteinases in wound healing by using BE16627B, a matrix metalloproteinase inhibitor. Identical surgical procedures consisting of a colonic anastomosis (single-layer, inverted) and implantation of an osmotic pump in the back were performed in male Sprague-Dawley rats weighing 270 to 290 grams. The animals were randomly assigned to receive either BE16627B (n = 10) dissolved in dimethylsulfoxide and diluted with ethylene glycol at a dosage of 2.4 mg/rat/day for 3 days or the vehicle solution alone (n = 11). The solutions were administered through the surgically implanted osmotic pumps. The animals were killed 4 days after surgery, and the colonic bursting pressure (mm Hg) and hydroxyproline concentration (μg/mg wet tissue, index of collagen) were measured. The administration of BE16627B enhanced colonic anastomotic healing, as measured by the increase in the colonic bursting pressure (160 ± 12 vs. 125 ± 7 mm Hg; P <0.05) and the increase in the soluble fraction of collagen (0.27 ± 0.01 vs. 0.21 ± 0.01 μg/mg wet tissue; P < 0.01) in the anastomosis. Histologic examination of the tissue revealed that the use of BE16627B resulted in the preservation of the multilayered colonic structure and increased the network of collagen between both ends of the colon in the thickening submucosal layer. These findings demonstrate that the inhibition of matrix metalloproteinase activity influences colonic anastomotic healing, indicating a potential mechanism for enhancing anastomotic healing.