© 2020 by the American Association for the Study of Liver Diseases. In this review, we summarize the structural hallmarks, expression patterns, covalent cross-linking activities, and modes of regulation of LOX family members and discuss the clinical potential of their inhibition to treat fibrosis in general and liver fibrosis in particular. Moreover, LOX family members other than LOXL2 may prove to be attractive therapeutic targets. However, this unexpected negative outcome may be related to the inefficient antibody, rather than to LOXL2, not qualifying as a relevant antifibrotic target. Recent disappointing clinical trials with a monoclonal antibody against LOXL2 (simtuzumab) in patients with pulmonary and liver fibrosis dampened enthusiasm for LOX family member inhibition. THE LOX Formed: 1996, Yonkers, New York Source for information on Lox.
It's Beautiful, The LOX get to shining with their new video for 'The Family.' Telling a tale of when blood. Inhibition of the LOX family as a whole and of LOX, LOXL1, and LOXL2 specifically has been shown to suppress fibrosis progression and accelerate its reversal in rodent models of cardiac, renal, pulmonary, and liver fibrosis. 1 The LOX are out here as a 'Family.' On the heels of their latest album Filthy America. Although the expression of most LOX family members is elevated in experimental liver fibrosis of diverse etiologies, their individual contribution to fibrosis is incompletely understood. These LOX family members catalyze cross-linking of collagens at the site of premetastatic niche, promoting BDMC recruitment and thus enhancing lung. Lysyl oxidase family members (LOX and LOXL1, LOXL2, LOX元, and LOXL4 ) are extracellular copper-dependent enzymes that play a key role in ECM cross-linking, but have also other intracellular functions relevant to fibrosis and carcinogenesis. Our results provide genetic evidence that common LOX variants lead to increased susceptibility to developing of KC.The cross-linking of structural extracellular matrix (ECM) components, especially fibrillar collagens and elastin, is strongly implicated in fibrosis progression and resistance to fibrosis reversal. Analysis of the second case-control panel provided further confirmation of the LOX involvement in the KC phenotype however a stronger association signal was identified at a different SNP rs2956540 (p=0.002), also located in the intron 4 of LOX. Allelic testing for association of rs10519694 genotyping data from the first case-control panel replicated results of the family-based analysis (p=0.0001). Further TDT analysis of SNPs in LOX identified preferentially untransmitted haplotype of SNPs rs3792803-rs10519694 located in the intron 4 of LOX to the affected family members (p=0.014) (Li, Tang, Rabinowitz ARVO 2008). Our prior genome-wide linkage scan identified a locus at 5q23.2, overlapping the LOX gene. Allelic testing for association was done under the additive model. Genotyping of the LOX SNPs was performed as part of a genome-wide association scan using Illumina’s CNV370-Quad beadchip and as a part of confirmation study using custom Illumina’s iSelect beadchip in two independent panels of case-control subjects, consisting of the 222 patients and 3324 controls, and 304 patients and 518 controls, respectively. Linkage was conducted in sib-pair families, with follow up association by Transmission Disequilibrium Test (TDT). Individuals with KC were diagnosed using both clinical signs and videokeratography.
To determine whether LOX is a genetic determinant of the pathogenesis of KC, we performed a comprehensive analysis of the common variants in LOX using case-control samples and compared the results to the linkage scan results of families with KC. Collagen cross-linking is being utilized as a new treatment for KC. The Lysyl Oxidase gene (LOX) encodes an enzyme responsible for collagen cross-linking in the cornea. Keratoconus (KC) is a bilateral non-inflammatory progressive corneal disorder with complex genetic inheritance.
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