Megalin and cubilin in the human gallbladder epithelium

Abstract

Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 +/- 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 +/- 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation.

Rare De Novo Copy Number Variants in Patients with Congenital Pulmonary Atresia

“…Interestingly, the anatomic malformations observed with PA in humans are consistent with the defects in the outflow tract in the zebrafish model [31], [32]. Cubilin, encoded by CUBN , is a receptor expressed in the apical pole of absorptive epithelia [33], and it plays an important role in the absorption of vitamin B 12 [34]. The interactions between folate, vitamin B 12 , and homocysteine are summarized in Figure 1C.…”

New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression

“…Gallstone disease is a multifactorial condition of the gallbladder, which involves genetic, sex, age and environmental variables (Lammert and Miquel, 2008). A study of a small number of gallstone patients in the Greek population found that both megalin and cubilin were downregulated in gallstone patients at the mRNA and protein levels (Tsaroucha et al, 2008). On the other hand, we have found that gallstone-susceptible mice fed a cholesterolrich lithogenic diet showed a reduction in megalin mRNA expression (Fig.…”

“…Megalin is also present in the kidney, lung and thyroid (Willnow et al, 1996;Lundgren et al, 1997;Marino et al, 1999), epydidimis (Hermo et al, 1999), mammary gland (Lundgren et al, 1997;Rowling et al, 2006) and gallbladder (Erranz et al, 2004;Tsaroucha et al, 2008).…”

The role of albumin receptors in regulation of albumin homeostasis: Implications for drug delivery

“…They are primarily expressed in polarized epithelial cells with a few exceptions. For instance, cubilin has been identified in several types of cells from different species, including epithelial cells from proximal tubules (rat [153], dog [59], mice and humans [150]), yolk sac (rat [153] and human [165]), small intestine (canine [166], rabbit [167], dog [168] and rat [163]), glomerular podocytes (rat and human [169]), inner ear (rat [170]), lung (human [171]), gallbladder (human [172]), mammary (murine and human [173]), uterus and oviduct (human [174]) as well as placental syncytiotrophoblasts and cytotrophoblasts (human [165]). In most cases, cubilin is co-expressed with megalin, where both are located at the apical membranes [167,[175][176][177].…”