Urokinase Stimulates Production of Matrix Metalloproteinase-9 in Fibroblasts with Involvement of Reactive Oxygen Species

Zubkova, Ekaterina; Menshikov, Mikhail; Плеханова, О. С.; Белоглазова, И. Б.; Ratner, E. I.; Парфенова, Е. В.

doi:10.1007/s10517-014-2481-5

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…Studies in fibroblasts have suggested that MMP expression may be influenced by changes in NADPH oxidase-1 (Nox-1) levels (Arbiser et al, 2002). Urokinase may affect MMP-9 expression partly through increasing the generation of ROS (Zubkova et al, 2014). Leukocytes are not only a major source of MMPs, but they also generate ROS that can influence MMP activity.…”

Section: Role Of Mmps In Vascular Pathologymentioning

confidence: 99%

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

Wang

Khalil

2018

Advances in Pharmacology

451

316

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by activation through removal of the propeptide domain from their latent zymogen form. MMPs are often secreted in an inactive proMMP form, which is cleaved to the active form by various proteinases including other MMPs. MMPs degrade various protein substrates in ECM including collagen and elastin. MMPs could also influence endothelial cell function as well as VSM cell migration, proliferation, Ca signaling, and contraction. MMPs play a role in vascular tissue remodeling during various biological processes such as angiogenesis, embryogenesis, morphogenesis, and wound repair. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension, preeclampsia, atherosclerosis, aneurysm formation, as well as excessive venous dilation and lower extremity venous disease. MMPs are often regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs may serve as biomarkers and potential therapeutic targets for certain vascular disorders.

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Section: Role Of Mmps In Vascular Pathologymentioning

confidence: 99%

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

Wang

Khalil

2018

Advances in Pharmacology

451

316

View full text Add to dashboard Cite

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“…MMP expression in fibroblasts depends on NADPH oxidase-1 expression (Arbiser et al, 2002). Also, urokinase may regulate MMP-9 expression by increasing ROS generation in fibroblasts (Zubkova et al, 2014). In addition to producing MMPs, leukocytes generate oxidants that can both activate (via oxidation of the prodomain thiol, followed by autolytic cleavage) and inactivate MMPs (via modification of amino acids critical for catalytic activity), providing a mechanism to control bursts of proteolytic activity (Fu et al, 2004).…”

Section: Inflammation and Mmps In Vvsmentioning

confidence: 99%

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

MacColl

Khalil

2015

J Pharmacol Exp Ther

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Lower-extremity veins have efficient wall structure and function and competent valves that permit upward movement of deoxygenated blood toward the heart against hydrostatic venous pressure. Matrix metalloproteinases (MMPs) play an important role in maintaining vein wall structure and function. MMPs are zinc-binding endopeptidases secreted as inactive pro-MMPs by fibroblasts, vascular smooth muscle (VSM), and leukocytes. ProMMPs are activated by various activators including other MMPs and proteinases. MMPs cause degradation of extracellular matrix (ECM) proteins such as collagen and elastin, and could have additional effects on the endothelium, as well as VSM cell migration, proliferation, Ca 21 signaling, and contraction. Increased lower-extremity hydrostatic venous pressure is thought to induce hypoxia-inducible factors and other MMP inducers/ activators such as extracellular matrix metalloproteinase inducer, prostanoids, chymase, and hormones, leading to increased MMP expression/activity, ECM degradation, VSM relaxation, and venous dilation. Leukocyte infiltration and inflammation of the vein wall cause further increases in MMPs, vein wall dilation, valve degradation, and different clinical stages of chronic venous disease (CVD), including varicose veins (VVs). VVs are characterized by ECM imbalance, incompetent valves, venous reflux, wall dilation, and tortuosity. VVs often show increased MMP levels, but may show no change or decreased levels, depending on the VV region (atrophic regions with little ECM versus hypertrophic regions with abundant ECM) and MMP form (inactive pro-MMP versus active MMP). Management of VVs includes compression stockings, venotonics, and surgical obliteration or removal. Because these approaches do not treat the causes of VVs, alternative methods are being developed. In addition to endogenous tissue inhibitors of MMPs, synthetic MMP inhibitors have been developed, and their effects in the treatment of VVs need to be examined.

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“…Another factor that acts during growth and maturation is the imbalance of these MMPs and possibly their tissue inhibitors (TIMPs; Dean et al, 1989;Bullen et al, 1995;Yu et al, 2013) and may lead to exacerbated degradation of matrix components. Although MMP-9 is predominantly secreted by inflammatory cells (Oshiro et al, 2003), MMP-9 is also produced in fibroblasts (Zubkova et al, 2014) indicating a high matrix remodeling during growth. MMP-9 in association with MMP-2, has the main role in the degradation of denatured collagen.…”

Section: Discussionmentioning

confidence: 99%

Morphological Alterations and Increased Gelatinase Activity in the Superficial Digital Flexor Tendon of Chickens During Growth and Maturation

Fêo

Biancalana

Nakagaki

et al. 2018

The Anatomical Record

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The superficial digital flexor tendon (SDFT) connects the superficial digital flexor muscle to the digits and its main function is to participate in digit flexion. The SDFT presents different regions along its length, which adapt to different biomechanical forces. During growth and maturation, the tendon may present changes in the regions subjected to compression and tension, with variations in the composition of the extracellular matrix (ECM), in the arrangement of collagen fibers and cellularity. With the purpose of analyzing the morphological and biochemical alterations of ECM of tendons during the growth and maturation, Gallus domesticus were euthanized at 1, 5, and 8 months of age and their SDFT were divided into regions of tension/compression (Sp) and tension (Sd). From 1 month of age, the Sp region already presented fibrocartilage characteristics with cells similar to chondrocytes. At 5 and 8 months, the Sd region displayed formation of a new structure similar to bone matrix, and intense metachromasia. The animals of 5 and 8 months presented an increase in MMP‐2 and ‐9 activities and a lower number of cells when compared with the animals of 1 month, in both regions. In conclusion, structural and biochemical alterations occur during the maturation process of the SDFT, involving a decrease in the number of cells and changes in the degradation and composition of the ECM. Anat Rec, 302:964–972, 2019. © 2018 Wiley Periodicals, Inc.

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Urokinase Stimulates Production of Matrix Metalloproteinase-9 in Fibroblasts with Involvement of Reactive Oxygen Species

Cited by 7 publications

References 14 publications

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease

Morphological Alterations and Increased Gelatinase Activity in the Superficial Digital Flexor Tendon of Chickens During Growth and Maturation

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