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Possible dual role of decorin in abdominal aortic aneurysm.

Ueda K, Yoshimura K, Yamashita O, Harada T, Morikage N, Hamano K - PLoS ONE (2015)

Bottom Line: Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers.In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages.The results suggest that decorin plays a dual role in AAA.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan.

ABSTRACT
Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP)-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion.

No MeSH data available.


Related in: MedlinePlus

Role of decorin in macrophage secretion of MMP-9.(A) Cultured mouse macrophages were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. (B) MMP-9 protein levels in the conditioned media were determined by gelatin zymography. Representative results are shown. (C-D) Cultured mouse macrophages were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses of MMP-9 (C) and TGF-β (D) are shown. TGF-β protein levels in the conditioned media were determined by enzyme-linked immunosorbent assay (ELISA). Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
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pone.0120689.g005: Role of decorin in macrophage secretion of MMP-9.(A) Cultured mouse macrophages were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. (B) MMP-9 protein levels in the conditioned media were determined by gelatin zymography. Representative results are shown. (C-D) Cultured mouse macrophages were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses of MMP-9 (C) and TGF-β (D) are shown. TGF-β protein levels in the conditioned media were determined by enzyme-linked immunosorbent assay (ELISA). Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.

Mentions: To understand the conflicting findings regarding the role of decorin in aortic walls, we investigated whether decorin positively regulates MMP-9 secretion in macrophages, the major inflammatory cell-type secreting MMP-9 in AAA walls [9,17] (Fig. 5A). Under basal conditions, MMP-9 was nearly undetectable in the conditioned media from cultured mouse macrophages. In response to LPS treatment, macrophages secreted detectable levels of MMP-9. Intriguingly, pre-treatment with exogenous decorin resulted in a dose-dependent increase in LPS-induced MMP-9 secretion (Fig. 5B-C). In addition, LPS treatment increased macrophage secretion of TGF-β, and pre-treatment with exogenous decorin further enhanced this secretion (Fig. 5D).


Possible dual role of decorin in abdominal aortic aneurysm.

Ueda K, Yoshimura K, Yamashita O, Harada T, Morikage N, Hamano K - PLoS ONE (2015)

Role of decorin in macrophage secretion of MMP-9.(A) Cultured mouse macrophages were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. (B) MMP-9 protein levels in the conditioned media were determined by gelatin zymography. Representative results are shown. (C-D) Cultured mouse macrophages were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses of MMP-9 (C) and TGF-β (D) are shown. TGF-β protein levels in the conditioned media were determined by enzyme-linked immunosorbent assay (ELISA). Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362951&req=5

pone.0120689.g005: Role of decorin in macrophage secretion of MMP-9.(A) Cultured mouse macrophages were pre-treated with or without 0.4, 4, or 40 μg/ml decorin, then stimulated with or without 100 ng/ml lipopolysaccharide (LPS) for 48 h. (B) MMP-9 protein levels in the conditioned media were determined by gelatin zymography. Representative results are shown. (C-D) Cultured mouse macrophages were pre-treated with or without 40 μg/ml decorin, then stimulated with or without 100 ng/ml LPS for 48 h. Quantitative analyses of MMP-9 (C) and TGF-β (D) are shown. TGF-β protein levels in the conditioned media were determined by enzyme-linked immunosorbent assay (ELISA). Data are mean ± SD. **p<0.01 compared to Control; ##p<0.01 compared to LPS.
Mentions: To understand the conflicting findings regarding the role of decorin in aortic walls, we investigated whether decorin positively regulates MMP-9 secretion in macrophages, the major inflammatory cell-type secreting MMP-9 in AAA walls [9,17] (Fig. 5A). Under basal conditions, MMP-9 was nearly undetectable in the conditioned media from cultured mouse macrophages. In response to LPS treatment, macrophages secreted detectable levels of MMP-9. Intriguingly, pre-treatment with exogenous decorin resulted in a dose-dependent increase in LPS-induced MMP-9 secretion (Fig. 5B-C). In addition, LPS treatment increased macrophage secretion of TGF-β, and pre-treatment with exogenous decorin further enhanced this secretion (Fig. 5D).

Bottom Line: Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers.In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages.The results suggest that decorin plays a dual role in AAA.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan.

ABSTRACT
Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP)-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion.

No MeSH data available.


Related in: MedlinePlus