Lysyl oxidase like‐1 dysregulation and its contribution to direct inguinal hernia

Pascual, Gemma; Rodríguez, Marta; Mecham, Robert P.; Sommer, Pascal; Buján, Julia; Bellón, Juan M.

doi:10.1111/j.1365-2362.2009.02099.x

Cited by 26 publications

(18 citation statements)

References 25 publications

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“…Accordingly, our group and others have described a significant association between PEX and systemic disorders of elastic tissues, that is, aortic aneurysms, coronary artery ectasia, renal artery stenosis and pelvic organ prolapse67839404142. Changes in LOXL1 gene expression have been observed in many other conditions, including aging4344 and disorders involving weakening of elastic connective tissues454647.…”

Section: Discussionmentioning

confidence: 89%

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1

et al. 2017

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Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.

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Section: Discussionmentioning

confidence: 89%

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1

et al. 2017

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“…The interrelationship between these three factors is not fully established. However, it seems that there is reduced collagen synthesis by the fibroblasts 43,44 , decreased hydroxylation 32 , decreased cross-linking 46,47 and/or increased MMP activity 32,55,65,67,73 , causing accelerated collagen breakdown (Fig. 2).…”

Section: Discussionmentioning

confidence: 94%

“…Lysyl oxidases are copper dependent, and a study of the copper level in plasma and hernia sacs showed that the amount of copper was significantly lower in patients with a direct inguinal hernia than in people with an indirect inguinal hernia, which might reduce the lysyl oxidase activity 46 . The level of lysyl oxidase-like 1 was significantly lower in patients with a direct inguinal hernia than in controls 47 . Reduced lysyl oxidase activity and thereby reduced cross-linking might contribute to unstable collagen in patients with a hernia, and it would be worthwhile expanding clinical studies to assess the role of lysyl oxidase in hernia formation.…”

Section: Stability Of Collagenmentioning

confidence: 98%

Connective tissue alteration in abdominal wall hernia

Henriksen

Yadete

Sørensen

et al. 2011

Journal of British Surgery

131

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“…However, both clinical and basic research results indicate that the abnormal collagen synthesis and/or metabolism may play an important role in the pathological procedure of hernias [5][6][7][8]. Collagen is an important structural protein of connective tissues and a major component of the extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Liu

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Hernia is a disease with defects in collagen synthesis/metabolism. However, the underlying mechanisms for hernia formation have not been fully defined. Tamoxifen is a selective estrogen receptor modulator and used for patients with breast cancer. Tamoxifen also has pleiotropic and side effects. Herein, we report that tamoxifen treatment resulted in an appearance of a large bulge in the low abdomen between the hind legs in male but not in female mice. The autopsy demonstrated that the low abdominal wall was broken and a large amount of intestine herniated out of the abdominal cavity. Histological analysis indicated that tamoxifen caused structural abnormalities in the low abdominal wall which were associated with decreased type II collagen content. Furthermore, we determined increased matrix metalloproteinase-2 (MMP-2) and MMP-13 expression in the tissue. In vitro, tamoxifen induced MMP-2 and MMP-13 expression in fibroblasts. The promoter activity analysis and ChIP assay demonstrate that induction of MMP-13 expression was associated with activation of JNK-AP-1 and ERK1/2 signaling pathways while induction of MMP-2 expression was related to activation of the ERK1/2 signaling pathway. Taken together, our study establishes a novel murine hernia model, defines a severe side effect of tamoxifen, and suggests a caution to male patients receiving tamoxifen treatment.

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Lysyl oxidase like‐1 dysregulation and its contribution to direct inguinal hernia

Abstract: Our findings suggest that impaired elastic fibre function in the transversalis fascia of patients with direct inguinal hernia, reflected by diminished elastin synthesis and its enhanced enzyme degradation, contributes to the development of this type of hernia.

Cited by 26 publications

References 25 publications

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1

Connective tissue alteration in abdominal wall hernia

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

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