Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin.

Published on Oct 22, 2019in International Journal of Molecular Sciences4.556
· DOI :10.3390/IJMS20205234
Ursula Mirastschijski20
Estimated H-index: 20
(University of Bremen),
Blaž Lupše1
Estimated H-index: 1
(University of Bremen)
+ 11 AuthorsMagnus S. Ågren42
Estimated H-index: 42
Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced (p < 0.001) in KO skin explants compared to WT control skin but did not differ (p = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group (p = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice.
Figures & Tables
📖 Papers frequently viewed together
10 Citations
24 Citations
#1Magnus S. Ågren (UCPH: University of Copenhagen)H-Index: 7
#1Magnus S. Ågren (UCPH: University of Copenhagen)H-Index: 42
Last. Ulrich auf dem Keller (DTU: Technical University of Denmark)H-Index: 35
view all 2 authors...
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 bi...
7 CitationsSource
#1Ursula Mirastschijski (University of Bremen)H-Index: 20
#2Nilima Dinesh (University of Bremen)H-Index: 1
Last. Sørge Kelm (University of Bremen)H-Index: 34
view all 8 authors...
Matrix metalloproteinases (MMP) are a family of more than 25 zinc-dependent enzymes that are centrally involved in cellular migration, tissue remodelling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation. Subclasses of MMPs include collagenases, gelatinases, stromelysins, membrane-bo...
7 CitationsSource
#1Holly M. Lauridsen (Yale University)H-Index: 8
#2Amanda S. Pellowe (Yale University)H-Index: 4
Last. Anjelica L. Gonzalez (Yale University)H-Index: 13
view all 8 authors...
Sweet syndrome (SS) is a prototypical neutrophilic dermatosis, a class of inflammatory diseases marked by elevated levels of tumor necrosis factor (TNF)-α and IL-17A, pathologic neutrophil recruitment, and microvascular remodeling. Histologic analyses of four matrix proteins—collagen I and IV, laminin, and fibronectin—in skin biopsies of patients with SS reveal that the basement membrane of dermal postcapillary venules undergoes changes in structure and composition. Increased neutrophil recruitm...
12 CitationsSource
#1Kazuhiro Yamamoto (University of Oxford)H-Index: 17
#2Hiroshi Okano (University of Oxford)H-Index: 1
Last. Hideaki Nagase (University of Oxford)H-Index: 103
view all 11 authors...
Matrix metalloproteinase 13 (MMP-13) degrades collagenous extracellular matrix and its aberrant activity associates with diseases such as arthritis, cancer, atherosclerosis and fibrosis. The wide range of MMP-13 proteolytic capacity suggests that it is a powerful, potentially destructive proteinase and thus it has been believed that MMP-13 is not produced in most adult human tissues in the steady state. Present study has revealed that human chondrocytes isolated from healthy adults constitutivel...
74 CitationsSource
#1Maryam G. Rohani (Cedars-Sinai Medical Center)H-Index: 10
#2William C. Parks (Cedars-Sinai Medical Center)H-Index: 88
Abstract Repair following injury involves a range of processes – such as re-epithelialization, scar formation, angiogenesis, inflammation, and more – that function, often together, to restore tissue architecture. MMPs carry out diverse roles in all of these activities. In this article, we discuss how specific MMPs act on ECM during two critical repair processes: re-epithelialization and resolution of scar tissue. For wound closure, we discuss how two MMPs – MMP1 in human epidermis and MMP7 in mu...
191 CitationsSource
#1Magnus S. Ågren (UCPH: University of Copenhagen)H-Index: 42
#2Reinhild Schnabel (MHH: Hannover Medical School)H-Index: 5
Last. Ursula Mirastschijski (University of Bremen)H-Index: 20
view all 4 authors...
Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10 ng/ml) in the absence or presence of the nonselective MMP inhibitor GM6001 for 8 days. The basal culture conditions promoted type I collagen catabolism that was accelerated by TNF-α (p < 0.005) and accomplished by MMP...
49 CitationsSource
#1Eun-Jung Lee (Ewha Womans University)H-Index: 16
#2Pyong-Gon MoonH-Index: 12
Last. Hee-Sun Kim (Ewha Womans University)H-Index: 47
view all 4 authors...
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate cell-matrix composition and are also involved in processing various bioactive molecules such as cell-surface receptors, chemokines, and cytokines. Our group recently reported that MMP-3, -8, and -9 are upregulated during microglial activation and play a role as proinflammatory mediators (Lee et al., 2010, 2014). In particular, we demonstrated that MMP-8 has tumor necrosis factor alpha (TNF-α)-converting enzyme (TACE...
10 CitationsSource
#1Amin Ardestani (University of Bremen)H-Index: 18
#2Federico Paroni (University of Bremen)H-Index: 6
Last. Kathrin Maedler (University of Bremen)H-Index: 40
view all 12 authors...
Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20–like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets a...
130 CitationsSource
#1Su-Jin Ahn (Kyung Hee University)H-Index: 11
#2Eun-Mi Rhim (St. Paul's Hospital)H-Index: 2
Last. Sang Hyuk Park (Kyung Hee University)H-Index: 11
view all 7 authors...
Background: Various biologic mediators, including matrix metalloproteinases (MMPs), that are implicated in periodontal tissue breakdown can be induced by cytokines. MMPs are known to degrade periodontal ligament attachment, and bone matrix proteins and tissue inhibitors of metalloproteinase (TIMPs) inhibit the activity of MMPs. The aim of this study is to investigate the effect of tumor necrosis factor (TNF)-α on the expression of MMPs in human periodontal ligament (PDL) cells in vitro and estab...
18 CitationsSource
#2rabbitsH-Index: 1
#3M Mähler (Pasteur Institute)H-Index: 1
Last. Marcello RaspaH-Index: 14
view all 8 authors...
The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the ...
277 CitationsSource
Cited By8
#1Tanya Pulido (Buck Institute for Research on Aging)H-Index: 2
#2Michael C. Velarde (UP: University of the Philippines Diliman)H-Index: 5
Last. Fatouma Alimirah (Buck Institute for Research on Aging)H-Index: 8
view all 3 authors...
Abstract null null Wound healing is impaired with advanced age and certain chronic conditions, such as diabetes and obesity. Moreover, common cancer treatments, including chemotherapy and radiation, can cause unintended tissue damage and impair wound healing. Available wound care treatments are not always effective, as some wounds fail to heal or recur after treatment. Hence, a more thorough understanding of the pathophysiology of chronic, nonhealing wounds may offer new ideas for the developmen...
#1Ming ZhaoH-Index: 2
#2Jihong ShiH-Index: 13
Last. Dahai HuH-Index: 26
view all 8 authors...
Graphene is a new type of carbon nanomaterial discovered after fullerene and carbon nanotube. Due to the excellent biological properties such as biocompatibility, cell proliferation stimulating, and antibacterial properties, graphene and its derivatives have become emerging candidates for the development of novel cutaneous wound dressings and composite scaffolds. On the other hand, pre-clinical research on exosomes derived from mesenchymal stem cells (MSC-Exos) has been intensified for cell-free...
#1Yi-En Lu (KMU: Kaohsiung Medical University)H-Index: 1
#2Ying-Jung Chen (KMU: Kaohsiung Medical University)H-Index: 1
Abstract The aim of this study was to explore the signaling pathways associated with the effects of tumor necrosis factor alpha (TNF-α) on matrix metalloproteinase-1 (MMP-1) and MMP-3 expression in the human dermal fibroblast cell line CCD-966SK. TNF-α upregulated MMP-1 and MMP-3 mRNA and protein expression, and NF-κB/p65 activation was found to be involved in TNF-α-induced MMP-1 and MMP-3 upregulation. TNF-α induced p65 phosphorylation at Ser536 and acetylation at Lys310. p300 knockdown suppres...
2 CitationsSource
#1Nithya Subrahmanyam (UofU: University of Utah)H-Index: 5
#2Hamidreza Ghandehari (UofU: University of Utah)H-Index: 66
The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the ECM holds opportunities for cancer therapy on several fronts. There are targets in the tumor-associated ECM at the level of signaling molecules, enzyme expression, protein structure, receptor interactions, ...
1 CitationsSource
#1Luca Bini (UNISI: University of Siena)H-Index: 1
#1Luca Bini (UNISI: University of Siena)H-Index: 37
Last. Laura Bianchi (UNISI: University of Siena)H-Index: 21
view all 8 authors...
Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease...
1 CitationsSource
#1Jin ShuH-Index: 1
Last. Haiya Wang (SJTU: Shanghai Jiao Tong University)H-Index: 1
view all 4 authors...
Angiotensin II (AngII) is a central signaling molecule of the renin‑angiotensin system that serves a vital role in myocardial fibrosis (MF). The present study aimed to investigate the effects of matrix metalloproteinase (MMP)3 on MF progression. To induce cellular fibrosis, H9C2 rat myocardial cells were treated with AngII for 24 h. Subsequently, cells were treated with levocarnitine, or transfected with small interfering (si)RNA‑negative control or siRNA‑MMP3 (1/2/3). Cell viability, apoptosis ...
1 CitationsSource
#1Fatima Zamri (Academic Center for Dentistry Amsterdam)H-Index: 1
#2Teun J. de Vries (Academic Center for Dentistry Amsterdam)H-Index: 28
The inflammatory disease rheumatoid arthritis (RA) and periodontitis show similarities in misbalances of cytokine levels, such as tumor necrosis factor-α (TNF-α). RA has been treated for two decades with TNF-α inhibitors which are effective by blocking TNF-α’s destructive action. Since RA and periodontitis show similarities in high levels of TNF-α, the periodontal status of RA patients may improve with the use of anti-TNF-α therapy. To assess this, a systematic review with special emphasis on du...
6 CitationsSource
#1Magnus S Ågren (UCPH: University of Copenhagen)H-Index: 6
#1Magnus S. Ågren (UCPH: University of Copenhagen)H-Index: 42
Last. Ulrich auf dem Keller (DTU: Technical University of Denmark)H-Index: 35
view all 2 authors...
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 bi...
7 CitationsSource
#1Alper Çıraklı (Ordu University)H-Index: 5
#1Alper Çıraklı (Ordu University)H-Index: 3
Last. Orhan Baş (Ordu University)H-Index: 8
view all 6 authors...
OBJECTIVES This study aims to evaluate the effect of tranexamic acid (TXA) application in tendon healing by using its immunohistochemical effects on tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and transforming growth factor-beta (TGF-β) expression; and to identify if TNF-α, MMP-3, and TGF-β can be used to monitor and evaluate tendon healing or not in tenotomized rat Achilles tendons. MATERIALS AND METHODS Twelve male Wistar-Albino rats (age 6-7-month-old; weighing 30...