mRNA Expression of Lysyl Oxidase and Matrix Metalloproteinase-12 in Mouse Skin

Mizobe, Yurika; Oikawa, Daichi; Tsuyama, Shoichiro; Akimoto, Yoriko; Hamasu, Kousuke; Onitsuka, Eiichiro; Sato, Marc; Takahata, Yoshihisa; Morimatsu, Fumiki; Furuse, Mitsuhiro

doi:10.1271/bbb.80450

Cited by 7 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although MMP-9 is the main gelatinase produced by macrophages, MMP-12 is a macrophage elastase with little gelatinase activity. Among the MMPs produced by macrophages, MMP-12 could be the responsible proteinase that directly facilitates structural changes of elastic lamina resulting in flow-induced outward vascular remodeling (Ding and Gray, 2001; Mizobe et al , 2008). However, in our experiment, a lack of MMP-12 did not have a significant effect on flow-induced outward vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Flow-induced outward vascular remodeling involves structural reorganization of elastic lamina of the arterial wall. Therefore, in addition to MMP-9, another key MMP produced by macrophages, MMP-12 (macrophage elastase), may play a critical role in flow-induced outward vascular remodeling by directly facilitating structural changes of the elastic lamina (Guo et al 2008; Luttun and Carmeliet 2001); (Ding and Gray 2001; Mizobe et al 2008). We hypothesized that MMPs produced by inflammatory cells, such as macrophages, play critical roles in flow-induced outward remodeling of the common carotid artery in response to an increase in blood flow.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling

Ota

Kurihara

Tsou

et al. 2009

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling

Ota

Kurihara

Tsou

et al. 2009

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…The genes for elastin and fibrillin-1, which are major components of elastin-associated microfibrils, remain active throughout life, but at the same time, elastogenesis in adults becomes relatively low (9,10). The levels of LOX/LOXL mRNAs also decrease during adulthood (9)(10)(11)(12)(13)(14)(15). We have reported previously that affected elastin renewal due to altered LOXL2 expression may contribute to the pathogenesis of MDE (7).…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, adenovirus-mediated gene transfer of fibulin-5 gene is sufficient to regenerate elastic fibres in the mouse skin deficient in the fibulin-5 gene (15). Fibulin-4 deficiency in mice also leads to decreased tropoelastin expression; and a decrease in fibulin-4 expression may cause down-regulation of tropoelastin gene expression and impaired elastic-fibre formation (9)(10)(11)(12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Fibulin Protein Expression in Mid-dermal Elastolysis and Anetoderma: A Study of 23 Cases

Gambichler

Reininghaus²,

Skrygan³

et al. 2016

Acta Derm Venerol

View full text Add to dashboard Cite

Decreased lysyl oxidase-like 2 expression in mid-dermal elastolysis

Gambichler

Skrygan

2012

Arch Dermatol Res

View full text Add to dashboard Cite

Mid-dermal elastolysis (MDE) is a rare disorder that is histopathologically characterized by selective loss of elastic fibres in the mid-dermis. Aetiopathogenesis of MDE is still obscure. We report for the first time on the expression of lysyl oxidase-like (LOXL) proteins in lesional and non-lesional skin of a patient with reticular variant of MDE. Real-time RT-PCR and immunohistochemistry were performed for matrix metalloproteinase-2 (MMP2), MMP7, MMP9, LOXL1, LOXL2, and LOXL3. LOXL1 and LOXL3 mRNA levels in lesional skin did not substantially differ from mRNA levels measured in healthy skin. For LOXL2, however, we found decreased mRNA expression in lesional skin as compared to healthy skin. mRNA expression of MMP2 and MMP7 of lesional skin did not substantially differ from healthy skin. However, MMP9 mRNA expression was massively increased in lesional skin when compared to healthy skin. Immunohistochemistry confirmed the altered expression of LOXL2 and MMP9 in lesional skin. In conclusion, our preliminary data suggest that not only increased elastolytic activity (e.g. MMP9 up-regulation) but also affected elastin renewal due to reduced LOXL expression may contribute to the pathogenesis of MDE. More research is warranted in MDE especially with regard to the LOX family, fibulins, fibrillins, and desmosines.

show abstract

mRNA Expression of Lysyl Oxidase and Matrix Metalloproteinase-12 in Mouse Skin

Cited by 7 publications

References 18 publications

Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling

Roles of Matrix Metalloproteinases in Flow-Induced Outward Vascular Remodeling

Fibulin Protein Expression in Mid-dermal Elastolysis and Anetoderma: A Study of 23 Cases

Decreased lysyl oxidase-like 2 expression in mid-dermal elastolysis

Contact Info

Product

Resources

About