Lysyl oxidase is involved in synovial hyperplasia and angiogenesis in rats with collagen-induced arthritis

Fan, Wei; Wan, Juan; Li, Qiuyan; Zhang, Mingzhu; Wan, Qiaofeng; Chen, Ji; Li, Haibo; Liu, Rongqing; Han, Mei

doi:10.3892/mmr.2017.7436

Cited by 6 publications

(7 citation statements)

References 28 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, our previous study on rheumatoid arthritis also found that LOX expression levels in synovial fluid were positively correlated with the expression levels of MMP-2 and MMP-9. Inhibition of LOX expression in rat synovial fluid can downregulate MMP-2 and MMP-9 expression levels15.…”

Section: Discussionmentioning

confidence: 99%

“…However, our previous study found that expression of LOX and MMP-2 are positively correlated in gastric cancer tissues, and they play synergistic roles in promoting the invasion and metastasis of gastric cancer14. Another of our previous studies, on rheumatoid arthritis, found that inhibition of LOX expression in rat synovial fluid can downregulate MMP-2 and MMP-9 expression15. The relationship between LOX and MMP-2 and MMP-9 in tumorigenesis and tumor progression are still unclear.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

LOX inhibition downregulates MMP-2 and MMP-9 in gastric cancer tissues and cells

Zhao¹,

Niu²,

Liu³

et al. 2019

J. Cancer

Self Cite

View full text Add to dashboard Cite

Objective: The objective of this study was to analyze the effects of lysyl oxidase (LOX) on the expression and enzyme activity of the matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and to study its preliminary effect mechanisms. Methods: We collected fresh cancer specimens from 49 gastric cancer patients who underwent surgery. Immunohistochemistry was used to quantitate the protein expression levels of LOX and MMP-9 in gastric cancer tissues and to analyze their correlation. Also, six-week old nude mice were divided into a control group and a LOX inhibition group. SGC-7901 gastric cancer cells were inoculated subcutaneously into the backs of the two groups of these mice to construct a gastric cancer-bearing nude mouse model. In the LOX inhibition group, β-aminopropionitrile (BAPN) was used to inhibit LOX. Western blotting was used to quantitate the relative expression levels of MMP-2 and MMP-9 in mouse tumor tissues, and gelatin zymography was used to quantitate their enzyme activity levels. In addition, BGC-823 gastric cancer cells were cultured, then 0.1 mM, 0.2 mM, and 0.3 mM BAPN and 2.5 nM, 5 nM, and 10 nM LOX were added to treat BGC-823 cells. ELISA and gelatin zymography were used to quantitate the protein concentrations and changes in enzyme activity of MMP-2 and MMP-9 in the culture supernatant. Western blotting was used to quantitate the relative expression levels of platelet derived growth factor receptor (PDGFR) in the BGC-823 gastric cancer cells after LOX inhibition and exogenous LOX addition. Results: In the tissues from the gastric cancer patients, the relative expression levels of LOX and MMP-9 were positively correlated (r = 0.326, P < 0.05). Compared with the control group, the tumor tissues from mice in the LOX inhibition group had reduced relative expression levels and enzyme activities of MMP-2 and MMP-9 (P < 0.05). After LOX were inhibited with different concentrations of BAPN in BGC-823 gastric cancer cells, the protein concentrations and enzyme activity levels of MMP-2 and MMP-9 in the culture supernatants were decreased (P < 0.05). In addition, the relative expression level of PDGFR in gastric cancer was decreased when BAPN concentrations increased, showing a negative dose-dependent manner (rPDGFRα = −0.964, rPDGFRβ = −0.988, P < 0.05). After exogenous LOX treating BGC-823 cells, the concentrations and enzyme activity levels of MMP-2 and MMP-9 in the cell supernatant were increased (P < 0.05). Further, the relative expression of PDGFR in gastric cancer cells was increased with the increase of exogenous LOX, showing a positive dose-dependent manner (rPDGFRα =0.952, rPDGFRβ =0.953, P<0.05). Conclusions: LOX inhibition can inhibit the expression and enzyme activity of MMP-2 and MMP-9 in gastric cancer tissues and cells, and the probable mechanism is through its effects on the PDGF-PDGFR signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

LOX inhibition downregulates MMP-2 and MMP-9 in gastric cancer tissues and cells

Zhao¹,

Niu²,

Liu³

et al. 2019

J. Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other evidence points to the involvement of lysyl oxidase (LOX) in the promotion of synovial hyperplasia and angiogenesis in CIA rats [ 43 ]. In this study, the researchers identified higher amounts of rough synovial membranes, higher microvascular density in those membranes and more synovial cell layers in CIA rats compared with saline-treated controls.…”

Section: Other Potentially Targetable Factors That Participate Inmentioning

confidence: 99%

Implications of Angiogenesis Involvement in Arthritis

MacDonald

Liu

et al. 2018

IJMS

159

117

View full text Add to dashboard Cite

Angiogenesis, the growth of new blood vessels, is essential in the pathogenesis of joint inflammatory disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA), facilitating the invasion of inflammatory cells and increase in local pain receptors that contribute to structural damage and pain. The angiogenic process is perpetuated by various mediators such as growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as proinflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases, and others. Despite the development of potent, well-tolerated nonbiologic (conventional) and biologic disease-modifying agents that have greatly improved outcomes for patients with RA, many remain resistant to these therapies, are only partial responders, or cannot tolerate biologics. The only approved therapies for OA include symptom-modifying agents, such as analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, and hyaluronic acid. None of the available treatments slow the disease progression, restore the original structure or enable a return to function of the damaged joint. Moreover, a number of safety concerns surround current therapies for RA and OA. New treatments are needed that not only target inflamed joints and control articular inflammation in RA and OA, but also selectively inhibit synovial angiogenesis, while preventing healthy tissue damage. This narrative review of the literature in PubMed focuses on the evidence illustrating the therapeutic benefits of modulating angiogenic activity in experimental RA and OA. This evidence points to new treatment targets in these diseases.

show abstract

“…In our previous study ( 17 ), the type II collagen-induced arthritis model of rats were established. BAPN was intraperitoneally injected to inhibit LOX activity.…”

Section: Discussionmentioning

confidence: 99%

“…The lysyl oxidase inhibitor β-aminopropionitrile (BAPN) impedes tumor angiogenesis and glioblastoma multiforme development in a mouse orthotopic brain tumor model ( 16 ). A previous study of our group indicated that inhibition of LOX attenuated the microvascular density in the synovial membranes of collagen-induced arthritis rats ( 17 ). In the present study we found that BAPN inhibited angiogenesis and migration of human umbilical vein endothelial cells (HUVECs).…”

Section: Introductionmentioning

confidence: 92%

Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration inï¿½vitro

et al. 2018

Self Cite

View full text Add to dashboard Cite

Lysyl oxidase (LOX) is an enzyme that oxidizes lysine residues in collagens and elastin. It stabilizes or remodels the extracellular matrix and basement membrane of blood vessels. Current oncology studies have revealed that LOX is upregulated in invasive cancer cells and bolstered cell movement, and LOX was observed to promote the angiogenesis and migration of endothelial cells. In the present study, angiogenesis and migration were examined in human umbilical vein endothelial cells (HUVECs). Following cell treatment with 0.1–0.4 mM β-aminoproprionitrile (BAPN), a specific inhibitor of LOX, angiogenesis was analyzed with a fibrin gel in vitro angiogenesis assay kit and migration was examined via a Boyden Chamber assay. Angiogenesis-associated gene expression was investigated with a microarray assay and confirmed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that HUVEC angiogenesis substantially increased in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and phorbol 12-myristate 13-acetate (PMA). In addition, LOX inhibition blocked the angiogenesis stimulated by VEGF bFGF and PMA, and the inhibition of LOX reduced the migration of HUVECs. Furthermore, the microarray and RT-qPCR revealed that BAPN downregulated myeloid progenitor inhibitory factor 1, and western blot analysis demonstrated that BAPN decreased the phosphorylation of MAPK and Akt, suggesting that the specific inhibitor of LOX, BAPN, may serve as an alternative strategy for preventing angiogenesis.

show abstract

Lysyl oxidase is involved in synovial hyperplasia and angiogenesis in rats with collagen-induced arthritis

Cited by 6 publications

References 28 publications

LOX inhibition downregulates MMP-2 and MMP-9 in gastric cancer tissues and cells

LOX inhibition downregulates MMP-2 and MMP-9 in gastric cancer tissues and cells

Implications of Angiogenesis Involvement in Arthritis

Lysyl oxidase inhibition via β-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration inï¿½vitro

Contact Info

Product

Resources

About