Biological role of matrix metalloproteinases: a critical balance

Löffek, Stefanie; Schilling, Oliver; Cw, Franzke

doi:10.1183/09031936.00146510

Cited by 626 publications

(418 citation statements)

References 121 publications

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“…ECM degradation is necessary for cellular migration and is carried out by MMPs and other proteases. In recent years, new studies have also shown that MMPs play a role in regulating extracellular tissue signaling networks [24]. Due to their destructive nature, the activity of these ECM proteases have to be controlled.…”

Section: Resultsmentioning

confidence: 99%

Influence of 660 and 830 nm Laser Irradiation on Genetic Profile of Extracellular Matrix Proteins in Diabetic Wounded Human Skin Fibroblast Cells

Houreld

2016

Proceedings of the 2016 International Conference on Biomedical and Biological Engineering

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Abstract. The extracellular matrix (ECM) provides tissue structural integrity and its synthesis plays a crucial role in wound healing. Impaired wound healing ensues following the destruction of the ECM, or the inhibition of its synthesis. An imbalance in ECM synthesis and degradation is seen in patients with diabetes. This has led to the development of novel therapies that aim to decrease ECM destruction and increase its synthesis. Photobiomodulation (PBM) has been shown to speed up the healing of these slow-to-heal wounds, and numerous studies are being conducted to determine the underlying molecular cause. This study aimed to ascertain the effect of laser irradiation at a wavelength of 660 or 830 nm at a dose of 5 J/cm 2 on the genetic expression profile of genes involved in ECM proteins. cDNA was reverse transcribed from total isolated RNA and used in real-time qualitative polymerase chain reaction (qPCR). Genes concerned with the basement membrane, collagen and ECM structural constituents, and ECM protesases and inhibitors were evaluated. Results showed that a similar genetic profile (although not identical) was seen post irradiation. PBM was able to reduce the expression of ECM proteases and increase mRNA levels of ECM proteins. This study fortifies the notion that PBM stimulates cellular activity and can influence ECM matrix synthesis and degradation during wound healing. This study has also shown that PBM is able to stimulate cells at a genetic level.

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Section: Resultsmentioning

confidence: 99%

Influence of 660 and 830 nm Laser Irradiation on Genetic Profile of Extracellular Matrix Proteins in Diabetic Wounded Human Skin Fibroblast Cells

Houreld

2016

Proceedings of the 2016 International Conference on Biomedical and Biological Engineering

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“…Since the early work on cloning and identifying MMPs (and their Metzincin relatives), we've uncovered many questions regarding their regulation at the gene and post-translational levels (47)(48)(49) (Fig. 7).…”

Section: Outlook For the Future: Looking Down The Trackmentioning

confidence: 99%

Riding the metalloproteinase roller coaster

Murphy

2017

Journal of Biological Chemistry

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To many of us in the field, working on matrix metalloproteinases (MMPs) has felt like riding a roller coaster, traveling through times of both excitement and despair. I was fortunate to join the ride when it was a mere carousel of three activities thought to target the proteins that comprise the extracellular matrix (ECM). New technologies brought the thrills of discovery as we uncovered specific proteinase genes and defined specialized activities in different cellular processes. The MMPs and the sister families of "a disintegrin and metalloproteinase" (ADAMs), ADAMs with thrombospondin domains (ADAM-TS), and Astacins are now recognized as key signaling "scissors" that drive rapid changes in a plethora of cellular pathways. My many excellent colleagues and collaborators and I were enthused to contribute to the early development of the field and continue to be amazed at its growth and sophistication. In contrast, the hype and failure of early inhibitor discovery have dogged our standing with the pharmaceutical industry and grant-giving bodies. However, the true believers have kept going, and knowledge of particular functions of MMPs and their contributions to disease progression has progressed. Recognition of the strategic importance of proteinase function should inspire more work harnessing new technologies such as imaging, proteomics, and gene editing to generate a more precise understanding of individual situations. New approaches to inhibitor design and assessment are possible, and the consequent ability to precisely abrogate specific MMP activity could contribute to the fight against a number of pathologies with unmet needs. What a ride it could be!

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“…Cystatins are structurally conserved, low molecular weight endogenous cysteine protease inhibitors found in most body compartments and fluids. Characteristically, they are described to function intra-and/or extracellularly to inhibit their target cysteine enzymes (for example, cathepsins) to maintain a crucial protease-inhibitor balance, thus regulating damaging proteolytic activities (2,3). Distinct cystatins regulate specific cysteine proteases.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory and Antibacterial Effects of Cystatin 9 against Francisella tularensis

Eaves-Pyles

Patel

Arigi

et al. 2013

Mol Med

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Cystatin 9 (CST9) is a member of the type 2 cysteine protease inhibitor family, which has been shown to have immunomodulatory effects that restrain inflammation, but its functions against bacterial infections are unknown. Here, we report that purified human recombinant (r)CST9 protects against the deadly bacterium Francisella tularensis (Ft) in vitro and in vivo. Macrophages infected with the Ft human pathogen Schu 4 (S4), then given 50 pg of rCST9 exhibited significantly decreased intracellular bacterial replication and increased killing via preventing the escape of S4 from the phagosome. Further, rCST9 induced autophagy in macrophages via the regulation of the mammalian target of rapamycin (mTOR) signaling pathways. rCST9 promoted the upregulation of macrophage proteins involved in antiinflammation and antiapoptosis, while restraining proinflammatory-associated proteins. Interestingly, the viability and virulence of S4 also was decreased directly by rCST9. In a mouse model of Ft inhalation, rCST9 significantly decreased organ bacterial burden and improved survival, which was not accompanied by excessive cytokine secretion or subsequent immune cell migration. The current report is the first to show the immunomodulatory and antimicrobial functions of rCST9 against Ft. We hypothesize that the attenuation of inflammation by rCST9 may be exploited for therapeutic purposes during infection.

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Biological role of matrix metalloproteinases: a critical balance

Cited by 626 publications

References 121 publications

Influence of 660 and 830 nm Laser Irradiation on Genetic Profile of Extracellular Matrix Proteins in Diabetic Wounded Human Skin Fibroblast Cells

Influence of 660 and 830 nm Laser Irradiation on Genetic Profile of Extracellular Matrix Proteins in Diabetic Wounded Human Skin Fibroblast Cells

Riding the metalloproteinase roller coaster

Immunomodulatory and Antibacterial Effects of Cystatin 9 against Francisella tularensis

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