pH dependence of the enzymatic processing of collagen I by MMP-1 (fibroblast collagenase), MMP-2 (gelatinase A), and MMP-14 ectodomain

Gioia, Magda; Fasciglione, Giovanni Francesco; Monaco, Susanna; Iundusi, Riccardo; Sbardella, Diego; Marini, Stefano; Tarantino, Umberto; Coletta, Massimo

doi:10.1007/s00775-010-0680-8

Cited by 30 publications

(17 citation statements)

References 41 publications

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“…Thus, during inflammation or cancer evolution pH of tissues changes quite drastically, bringing about either acidification and/or alkalinization. This may have important consequences for the interaction and the enzymatic properties of MMPs toward macromolecular substrates, as it has been observed in the case of collagen I (Gioia et al, 2010), putting in evidence as the change of pH may induce increase or decrease of the activity of different MMPs classes.…”

Section: Macromolecular Substratesmentioning

confidence: 87%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

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208

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Section: Macromolecular Substratesmentioning

confidence: 87%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

Self Cite

208

212

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“…The optimal pH for growth of common bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa has been reported to be close to neutral ( S. aureus : 7–7.5; P. aeruginosa : 6.5–7) with a minimum pH for growth being 4.2 and 5.6 and maximum 9.3 and 8, respectively . Bacterial contamination alters the pH of the wound bed due to increased lactate deposition, which in turn affects the expression of proinflammatory cytokines and matrix metalloproteinases . Prolonged over expression of these factors keeps the wound stuck in a self‐perpetuating inflammatory stage that may prohibit wound closure .…”

mentioning

confidence: 99%

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study

Kruse

Singh

Targosinski

et al. 2017

Wound Repair Regeneration

173

111

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Wound microenvironment plays a major role in the process of wound healing. It contains various external and internal factors that participate in wound pathophysiology. The pH is an important factor that influences wound healing by changing throughout the healing process. Several previous studies have investigated the role of pH in relation to pathogens but studies concentrating on the effects of pH on wound healing itself are inconclusive. The purpose of this study was to comprehensively and in a controlled fashion investigate the effect of pH on wound healing by studying its effect on human primary keratinocyte and fibroblast function in vitro and on wound healing in vivo. In vitro, primary human keratinocytes and fibroblasts were cultured in different levels of pH (5.5-12.5) and the effect on cell viability, proliferation, and migration was studied. A rat full-thickness wound model was used to investigate the effect of pH (5.5-9.5) on wound healing in vivo. The effect of pH on inflammation was monitored by measuring IL-1 α concentrations from wounds and cell cultures exposed to different pH environments. Our results showed that both skin cell types tolerated wide range of pH very well. They further demonstrated that both acidic and alkaline environments decelerated cell migration in comparison to neutral environments and interestingly alkaline conditions significantly enhanced cell proliferation. Results from the in vivo experiments indicated that a prolonged, strongly acidic wound environment prevents both wound closure and reepithelialization while a prolonged alkaline environment did not have any negative impact on wound closure or reepithelialization. Separately, both in vitro and in vivo studies showed that prolonged acidic conditions significantly increased the expression of IL-1 α in fibroblast cultures and in wound fluid, whereas prolonged alkaline conditions did not result in elevated amounts of IL-1 α.

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“…Matrix Metallopeptidase-2 (MMP-2), isolated from the culture media of rheumatoid arthritis synovial tissue32, is important for extracellular matrix degradation33. It has proteolytic activity against components of the basement membrane, preferentially cleaving collagen types I, IV, V, VII, and XI and gelatin63435. Recently, the association between MMP-2 and fluorosis has been explored22.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China

Pei

Liu

et al. 2017

Sci Rep

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Brick tea skeletal fluorosis is still a public health issue in the north-western area of China. However its pathogenesis remains unknown. Our previous study reveals that the severity of skeletal fluorosis in Tibetans is more serious than that in Kazaks, although they have similar fluoride exposure, suggesting the onset of brick tea type skeletal fluorosis might be genetically influenced. Here we show that MMP-2 rs2287074 SNP (G/A), but not rs243865, was associated with Brick tea type fluorosis in Tibetans and Kazaks, China. The trend test reveals a decline in probability for skeletal fluorosis with increasing number of A alleles in Tibetans. After controlling potential confounders, AA genotype had about 80 percent lower probability of developing skeletal fluorosis than GG genotype in Tibetans (odds ratio = 0.174, 95% CI: 0.053, 0.575), and approximately 53 percent lower probability in Kazaks (odds ratio = 0.462, 95% CI: 0.214, 0.996). A meta-analysis shows that the AA genotype had approximately 63 percent lower odds (odds ratio = 0.373, 95% CI: 0.202, 0.689) compared with GG genotype within the two ethnicities. A significant correlation was also found between the genotype of MMP2 rs2287074 and skeletal fluorosis severity. Therefore, the A allele of MMP2 rs2287074 could be a protective factor for brick tea skeletal fluorosis.

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pH dependence of the enzymatic processing of collagen I by MMP-1 (fibroblast collagenase), MMP-2 (gelatinase A), and MMP-14 ectodomain

Cited by 30 publications

References 41 publications

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study

Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China

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