The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes

Hannocks, Melanie-Jane; Zhang, Xueli; Gerwien, Hanna; Chashchina, Anna; Burmeister, Miriam; Korpos, Éva; Song, Jian; Sorokin, Lydia

doi:10.1016/j.matbio.2017.11.007

Cited by 130 publications

(95 citation statements)

References 91 publications

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“…The encoded protein of Mmp9 is matrix metallopeptidase 9. Mmp9 is involved in a wide range of biological functions including macrophage differentiation, inflammation, bone metabolism, and tumor invasion [27][28][29]. In our study, electric field stimulation resulted in a 6.53-fold increase in macrophage Mmp9, suggesting that dcEF stimulation may affect macrophage differentiation and inflammatory responses.…”

Section: Hub Genessupporting

confidence: 47%

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Liu

et al. 2020

IJMS

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At present, studies on macrophage proteins mainly focus on biological stimuli, with less attention paid to the responses of macrophage proteins to physical stimuli, such as electric fields. Here, we exploited the electric field-sensitive hub proteins of macrophages. RAW 264.7 macrophages were treated with a direct current electric field (dcEF) (200 mV/mm) for four hours, followed by RNA-Seq analysis. Differentially expressed genes (DEGs) were obtained, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and protein–protein interaction (PPI) analysis. Eight qPCR-verified DEGs were selected. Subsequently, three-dimensional protein models of DEGs were modeled by Modeller and Rosetta, followed by molecular dynamics simulation for 200 ns with GROMACS. Finally, dcEFs (10, 50, and 500 mV/mm) were used to simulate the molecular dynamics of DEG proteins for 200 ns, followed by trajectory analysis. The dcEF has no obvious effect on RAW 264.7 morphology. A total of 689 DEGs were obtained, and enrichment analysis showed that the steroid biosynthesis pathway was most affected by the dcEF. Moreover, the three-dimensional protein structures of hub proteins were constructed, and trajectory analysis suggested that the dcEF caused an increase in the atomic motion of the protein in a dcEF-intensity-dependent manner. Overall, we provide new clues and a basis for investigating the hub proteins of macrophages in response to electric field stimulation.

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Section: Hub Genessupporting

confidence: 47%

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Liu

et al. 2020

IJMS

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“…Under normal physiological conditions, MMPs are directly responsible for pathogenesis of cerebrovascular diseases and their activity is regulated by TIMPs 24 . The evidence showed that MMP-2 and MMP-9 might be up-regulated and activated during cerebral disease or stroke which are expressed particularly frequently in the nervous system 25 . MMP-2 also plays a significant role in the regulation of activity of platelets 26 , while MMP-9 damages matrix components of the basement membrane leading to neuro-inflammation after focal cerebral ischemia by maintaining the integrity of cerebral vasculature 27 .…”

Section: Discussionmentioning

confidence: 99%

The effect and mechanism of combination of total paeony glycosides and total ligustici phenolic acids against focal cerebral ischemia

Feng

Song

et al. 2020

Sci Rep

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The root of Paeonia lactiflora Pall. (Chishao, CS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) were widely used as a drug pair in Chinese Medicine, and the combination of CS and CX showed a more significant inhibition on neuronal apoptosis in our previous study. In the present study, total paeony glycosides (TPGs) from CS and total ligustici phenolic acids (TLPAs) from CX were combined to evaluate the synergistic effects against focal cerebral ischemia both in vitro and in vivo. The combination of TPGs and TLPAs at 7:3 had the best anti-oxidative stress and anti-inflammatory effect on OGD-induced HUVEC. Additionally, the infarction area proportion and neuron apoptosis of rats by TPGs:TLPAs (7:3) was significantly lower than their alone in MCAO rats. Moreover, TPGs: TLPAs of 7:3 showed a more significant effect on decreasing the expression of MMP-2 and MMP-9, and increasing the protein expression or mRNA level of TIMP-1 than other combinations. The optimal ratio of TPGs and TLPAs at 7:3 could bring more remarkable protective effects against focal cerebral ischemia in MCAO rats by alleviating oxidative stress, inflammatory and neuronal apoptosis to protect the blood-brain barrier. Overall, the present study provided benefical evidence for clinical application of CS and CX as a "drug pair". As the third highest worldwide cause of mortality 1 , stroke has been treated using antithrombotic therapy 2 , anticoagulant therapy 3,4 , neuroprotective and vascular dilated therapy. Numerous studies have demonstrated that the severity of neuronal apoptosis was associated with neurofunction, indicating a crucial role in the prognosis of ischemic stroke sufferer 5. Early anti-inflammatory and anti-oxidative stress may promote apoptosis of nerve cells. Thus attenuating these potential damage of nerve cells in ischemic area will be an effective strategy in clinical application. Chinese medicine (CM) has been used to treat stroke for a long time. Many classical prescriptions for treating cerebral diseases, such as Xiao-xu-ming decoction 6 are still being commonly used in modern clinial both in China and in other countries 7,8. Paeonia lactiflora Pall. (Chinese name: Chishao, CS) has been used worldwide for centuries and reported to exhibit various pharmacological bioactivities including anticoagulation, cognition enhancement, immunoregulatory 9 and anticance 10 , antioxidative 11 , and antidiabetic properties 12. The ischemic stroke protection of Paeoniae Radix may be related to its anti-oxidative stress and improvement of brain microcirculation. Ligusticum chuanxiong Hort. (Chinese name: Chuanxiong, CX) which belongs to the Umbelliferae family, is a valuable medicinal herb used worldwide and has been used for the treatment of atherosclerosis, hypertension, angina pectoris, and anti-inflammatory via acilitating blood circulation and dispersing blood stasis 13. Our previous study revealed the combination of CS and CX exerted more remarkable protective effects than alone by attenuating ER-stress-dependent apoptotic signaling and...

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“…Concerning the extracellular matrix in the dermis, it is known that in a normal condition, the ratio of types I and III collagen fibers in covered skin remained constant throughout childhood and young adult life [32]. However, it is interesting that collagen fibrils in the dermis are hybrid molecules formed by type I and type III collagen, in which type III collagen is located at the periphery of the collagen fibrils [33,34].…”

Section: Discussionmentioning

confidence: 99%

Initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin

et al. 2020

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Background: Calvaria skin has a reduced thickness, and its initial damage produced by irradiation was scarcely reported. We aimed to identify the initial effects of x-ray irradiation in the rat calvaria skin. Methods: After approval by the Animal Ethical Committee, calvaria skin sections of five Wistar rats per time point were evaluated on days 4, 9, 14, and 25 following a single 15-Gy x-ray irradiation of the head. The control group was composed of five rats and evaluated on day 4. Sections were assessed using hematoxylin-eosin and Masson's trichrome staining for morphology, inflammation, and fibrosis. Fibrosis was also evaluated by the collagen maturation index from Picrosirius red staining and by cell proliferation using the immunohistochemistry, after 5bromo-2-deoxyuridine intraperitoneal injection. Results: In irradiated rats, we observed a reduction in epithelial cell proliferation (p = 0.004) and in matrix metalloproteinase-9 expression (p < 0.001), an increase in the maturation index, and with a predominance in the type I collagen fibers, on days 9 and 14 (1.19 and 1.17, respectively). A progressive disorganization in the morphology of the collagen fibers at all time points and changes in morphology of the sebaceous gland cells and hair follicle were present until day 14. Conclusions: The initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin was a change in the normal morphology of collagen fibers to an amorphous aspect, a temporary absence of the sebaceous gland and hair follicles, and without a visible inflammatory process, cell proliferation, or fibrosis process in the dermis.

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The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes

Cited by 130 publications

References 91 publications

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

The effect and mechanism of combination of total paeony glycosides and total ligustici phenolic acids against focal cerebral ischemia

Initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin

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