Constant serum levels of secreted asialoglycoprotein receptor sH2a and decrease with cirrhosis

“…ADIPOQ is expressed in adipose tissue exclusively and modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation (Diez and Iglesias, 2003). ASGR1, encoding a subunit of the asialoglycoprotein receptor, plays a critical role in serum glycoprotein homeostasis (Benyair et al, 2011). FABP4 encodes the fatty acid-binding pro-tein found in adipocytes and delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus (Maeda et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of skeletal muscle at prenatal stages in Polled Dorset versus Small-tailed Han sheep

Liu

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The objectives of the present study were to identify additional genes that may play important roles in the regulation of skeletal muscle growth and development, and to provide fundamental information for understanding the underlying molecular mechanisms. Eighteen cDNA libraries were constructed from the longissimus muscle of Polled Dorset (PD) and Small-tailed Han (SH) fetuses. To reveal the differences between the two species, we analyzed the differences in gene expression in 60-, 90-and 120-day fetal skeletal muscle by applying Agilent ovine genome-wide microarray. In this study, we obtained 17,704 genes using a chip containing 39,242 probes. There were 88 differentially expressed genes in the 60-day group (P < 0.05), 128 genes in the 90-day group (P < 0.05), and 340 genes in the 120-day group (P < 0.05) between the two breeds. The differentially expressed genes were grouped in different GO categories and signaling pathways. These results suggested that there are many genetic differences in the muscle growth and development transcriptomes between these two breeds. This study laid the foundation for future genomic research in sheep.

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“…Several conditions correlate with a significant reduction in the levels of the ASGPR, among them hepatocyte dedifferentiation [6], [7], chronic alcohol consumption [8] and liver fibrosis and cirrhosis [9], [10]. We found that the levels of sH2a are also significantly reduced in a pilot evaluation of HCV patients with cirrhosis [3]. Therefore, we reasoned that sH2a might be regulated in a similar fashion as the membrane ASGPR and could constitute a unique non-invasive marker for hepatocyte function and fibrosis.…”

Section: Introductionmentioning

confidence: 92%

“…A soluble secreted form of the human asialoglycoprotein receptor (ASGPR), termed sH2a, is formed by cleavage in the endoplasmic reticulum of hepatocytes of its precursor [1] , encoded by an alternatively spliced variant of the ASGPR H2 subunit mRNA [2] . We recently reported that sH2a is present at constant levels in the serum of healthy individuals [3] . The ASGPR is expressed to a significant degree only in hepatocytes [4] and serves in the clearance of asialoglycoproteins from the plasma [5] .…”

Section: Introductionmentioning

confidence: 97%

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A Secreted Form of the Asialoglycoprotein Receptor, sH2a, as a Novel Potential Noninvasive Marker for Liver Fibrosis

Veselkin

Kondratyev²,

Lurie³

et al. 2011

PLoS ONE

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Background and AimThe human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function.MethodsWe measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals.ResultssH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86.ConclusionssH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

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Constant serum levels of secreted asialoglycoprotein receptor sH2a and decrease with cirrhosis

Abstract: Constant sH2a levels suggest constitutive secretion from hepatocytes in healthy individuals. This constant level and the decrease with cirrhosis suggest a diagnostic potential.

Cited by 10 publications

References 17 publications

Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD

Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD

Transcriptome analysis of skeletal muscle at prenatal stages in Polled Dorset versus Small-tailed Han sheep

A Secreted Form of the Asialoglycoprotein Receptor, sH2a, as a Novel Potential Noninvasive Marker for Liver Fibrosis

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