Anti-LRAT polyclonal antibody

Background/Objectives: Although there is strong evidence implicating genetic factors in congenital diaphragmatic hernia (CDH) pathogenesis, few causal genes have been identified. Many studies suggest that early disruption of the retinoid signaling pathway during gestation may contribute to CDH etiology. Chromosome abnormalities are detected in 10-20% of CDH cases. Chromosomal regions that are involved in balanced translocations or are recurrently deleted or duplicated in patients with CDH are of particular interest to researchers because they are more likely to harbor genes that cause or predispose one to the development of CDH. The aim of this review was to select chromosome loci which have been shown to be associated with CDH and to investigate if these loci contain candidate genes involved in the retinoic signaling pathway. Data Sources: We have re-examined the known CDH-critical chromosomal loci and searched in available databases, such as the UCSC Genome Browser and OMIM, to see whether candidate genes related to the retinoid pathway were present within these loci. Results: Twelve retinoid-related genes have been proposed as potential candidates. Among them, COUP-TFII, FOG2 and GATA4 have already been well studied, especially in animal models. We propose other candidates such as STRA6, LRAT, CRBP1, CRBP2 and CRABP1 are directly implicated in retinoic acid metabolism. Conclusion: The identification of CDH-related genes and pathways affecting a normal diaphragm will contribute to the understanding of the pathophysiology of this severe embryopathy and might help to facilitate prenatal management and devise more individual treatment strategies. Further studies are necessary to screen large cohorts of patients with CDH for microimbalances or de novo mutations in these candidate genes. Moreover, functional analyses are needed to establish their exact role in CDH etiology. Copyright (C) 2010 S. Karger AG, Basel

The mechanisms of retinol transport and accumulation in hepatic stellate cells (HSC) remain to be elucidated. Our previous studies suggested that retinol esterification activity, particularly lecithin: retinol acyltransferase (LRAT) activity, in liver retinoid metabolism is important to elucidate the relationship between retinol uptake by HSC and the esterification of retinol. In the present study, using a human HSC-like cell line, LI90, we demonstrated that retinol esterification activity of LI90 cells is similar to that of primary cultures of rat HSC and higher than that of a human hepatoma cell line. Further, since progesterone or diphospho-lauroyl-phosphatidylcholine increased retinol esterification activity of LI90 cells, it is likely that LRAT contributes to retinol esterification in LI90. We examined retinol esterification in LI90 cells and clearance of retinol from culture medium. The percentages of both retinol and esterified retinol in LI90 cells increased in a manner dependent on retinol concentration in medium, whereas that of retinol in medium decreased. The percentages of esterified and unesterified retinol in LI90 cells and of retinol in medium were linearly dependent on the logarithm of the initial concentration of retinol in the medium. These results suggest that retinol esterification activity contributes to retinol uptake by HSC and maintenance of non-toxic retinol levels in plasma.