Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae

doi:10.1016/j.taap.2012.01.026

Cited by 26 publications

(34 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies also demonstrate that Hcy upregulates VEGF production in macrophages via NF-κB activation (Kiriakidis et al, 2003;Maeda, Yamamoto, Fujio, & Azuma, 2003). More recently, a study by Lee et al suggested that Hcy treatment resulted in elevated MMP-9 production in the J774A.1 murine macrophage cell line (Lee et al, 2012). 12 hours of 300µM Hcy treatment resulted in significantly elevated MMP-9 protein expression and activity.…”

Section: Macrophages and Hyperhomocysteinemiamentioning

confidence: 97%

“…Hcy stimulates MMP-9 production in several cell types including ventricular endothelial cells, brain endothelial cells and macrophages. Studies suggest that Hcy largely upregulates MMP-9 expression in these cell lines through an oxidative stress induced ERK/AP-1 pathway (Lee et al, 2012;Moshal et al, 2006;Tyagi et al, 2009). …”

Section: Mmp-9 and Hyperhomocysteinemiamentioning

confidence: 99%

“…Hyperhomocysteinemia is a well-known stimulus for MMP-9 activity (Lee et al, 2012;Moshal et al, 2006;Tyagi et al, 2009) and strongly correlates with its activity in vascular disease (Wiernicki et al, 2011). Hcy stimulates MMP-9 production in several cell types including ventricular endothelial cells, brain endothelial cells and macrophages.…”

Section: Mmp-9 and Hyperhomocysteinemiamentioning

confidence: 99%

“…reactive oxygen species (ROS), matrix metalloproteinase-9 and stimulation of macrophage migration through chemotaxis (Lee et al, 2012;Tyagi et al, 2009;Wang et al, 2001). MMP-9 is an endoproteinase that degrades collagen within the ECM.…”

Section: Introductionmentioning

confidence: 99%

“…The ability of HHcy to induce high levels of reactive oxygen species (ROS) indicates that Hcy may inflict a great deal of damage through increased oxidative stress and inflammation (Hayden & Tyagi, 2004;Signorello et al, 2007; S. C. Tyagi, Lominadze, & Roberts, 2005). HHcy is also known to increase the expression and activity of matrix metalloproteinases (MMP), particularly MMP-9 (Seung Jin Lee et al, 2012;Moshal et al, 2006;Neetu Tyagi et al, 2009). MMP-9 is an endoproteinase that degrades components of the extracellular matrix (ECM).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Exercise mitigates the effects of hyperhomocysteinemia on adverse skeletal muscle remodeling.

Winchester¹

View full text Add to dashboard Cite

Intro Hyperhomocysteinemia (HHcy) is associated with vascular and skeletal muscle dysfunction. HHcy induces MMP‐9 activity, myostatin release, systemic inflammation and may increase M1 macrophages. Previous reports suggest that exercise reduces HHcy and myostatin levels, however the effects of exercise on macrophages and myostatin during HHcy are unclear. We hypothesize that exercise decreases HHcy induced inflammation and muscular dysfunction by decreasing MMP‐9, myostatin and M1 macrophages. Methods C57 WT, FVB, MMP‐9‐/‐, CBS‐/+ (HHcy), and CBS‐/+/MMP‐9‐/‐ (Double KO) mice were administered 4 weeks of treadmill running, swimming, or no exercise for controls. Ultrasonography and laser Doppler were used to measure wall to lumen ratio, blood flow and perfusion rate of the femoral artery. Western Blotting, IHC, Histology and PCR were used to analyze mouse tissue samples. Results Blood flow rates in control CBS‐/+ mice were approximately 23.9% lower than in control C57 WT mice. This rate was increased by 1.89 fold with exercise. Wall to Lumen ratio was approximately 4.14 fold higher in the CBS‐/+ control mice compared with WT, but became similar to WT after exercise. Laser Perfusion imaging demonstrated a 12.5% lower femoral artery red blood cell flux in CBS‐/+ mice when compared with WT, but was increased by 1.35 fold after exercise. Collagen staining reveals higher collagen deposition in the gastrocnemius of CBS‐/+ mice compared with WT, but was completely reversed with exercise. Conclusions We conclude that Exercise Mitigates HHcy Induced Vascular Dysfunction and Adverse Skeletal Muscle Remodeling.

show abstract

Section: Macrophages and Hyperhomocysteinemiamentioning

confidence: 97%

Section: Mmp-9 and Hyperhomocysteinemiamentioning

confidence: 99%

Section: Mmp-9 and Hyperhomocysteinemiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Exercise mitigates the effects of hyperhomocysteinemia on adverse skeletal muscle remodeling.

Winchester¹

View full text Add to dashboard Cite

show abstract

A Distinct Macrophage Subset Mediating Tissue Destruction and Neovascularization in Giant Cell Arteritis: Implication of the YKL‐40/Interleukin‐13 Receptor α2 Axis

Sleen

Jiemy

Pringle

et al. 2021

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. Macrophages mediate inflammation, angiogenesis, and tissue destruction in giant cell arteritis (GCA). Serum levels of the macrophage-associated protein YKL-40 (chitinase 3-like protein 1), previously linked to angiogenesis and tissue remodeling, remain elevated in GCA despite glucocorticoid treatment. This study was undertaken to investigate the contribution of YKL-40 to vasculopathy in GCA.Methods. Immunohistochemistry was performed on GCA temporal artery biopsy specimens (n = 12) and aortas (n = 10) for detection of YKL-40, its receptor interleukin-13 receptor α2 (IL-13Rα2), macrophage markers PU.1 and CD206, and the tissue-destructive protein matrix metalloproteinase 9 (MMP-9). Ten noninflamed temporal artery biopsy specimens served as controls. In vitro experiments with granulocyte-macrophage colony-stimulating factor (GM-CSF)-or macrophage colony-stimulating factor (M-CSF)-skewed monocyte-derived macrophages were conducted to study the dynamics of YKL-40 production. Next, small interfering RNA-mediated knockdown of YKL-40 in GM-CSF-skewed macrophages was performed to study its effect on MMP-9 production. Finally, the angiogenic potential of YKL-40 was investigated by tube formation experiments using human microvascular endothelial cells (HMVECs).Results. YKL-40 was abundantly expressed by a CD206+MMP-9+ macrophage subset in inflamed temporal arteries and aortas. GM-CSF-skewed macrophages from GCA patients, but not healthy controls, released significantly higher levels of YKL-40 compared to M-CSF-skewed macrophages (P = 0.039). In inflamed temporal arteries, IL-13Rα2 was expressed by macrophages and endothelial cells. Functionally, knockdown of YKL-40 led to a 10-50% reduction in MMP-9 production by macrophages, whereas exposure of HMVECS to YKL-40 led to significantly increased tube formation. Conclusion.In GCA, a GM-CSF-skewed, CD206+MMP-9+ macrophage subset expresses high levels of YKL-40 which may stimulate tissue destruction and angiogenesis through IL-13Rα2 signaling. Targeting YKL-40 or GM-CSF may inhibit macrophages that are currently insufficiently suppressed by glucocorticoids.

show abstract

Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy

et al. 2017

View full text Add to dashboard Cite

A detrimental consequence of hypermethylation is hyperhomocysteinemia (HHcy), that causes oxidative stress, inflammation, and matrix degradation, which leads to multi-pathology in different organs. Although, it is well known that hypermethylation leads to overall gene silencing and hypomethylation leads to overall gene activation, the role of such process in skeletal muscle dysfunction during HHcy condition is unclear. In this study, we emphasized the multiple mechanisms including epigenetic alteration by which HHcy causes skeletal muscle myopathy. This review also highlights possible role of methylation, histone modification, and RNA interference in skeletal muscle dysfunction during HHcy condition and potential therapeutic molecules, putative challenges, and methodologies to deal with HHcy mediated skeletal muscle dysfunction. We also highlighted that B vitamins (mainly B12 and B6), with folic acid supplementation, could be useful as an adjuvant therapy to reverse these consequences associated with this HHcy conditions in skeletal muscle. However, we would recommend to further study involving long-term trials could help to assess efficacy of the use of these therapeutic agents. J. Cell. Biochem. 118: 2108-2117, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

Cited by 26 publications

References 41 publications

Exercise mitigates the effects of hyperhomocysteinemia on adverse skeletal muscle remodeling.

Exercise mitigates the effects of hyperhomocysteinemia on adverse skeletal muscle remodeling.

A Distinct Macrophage Subset Mediating Tissue Destruction and Neovascularization in Giant Cell Arteritis: Implication of the YKL‐40/Interleukin‐13 Receptor α2 Axis

Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy

Contact Info

Product

Resources

About