Phosphatidylcholine Passes by Paracellular Transport to the Apical Side of the Polarized Biliary Tumor Cell Line Mz-ChA-1
1
Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, D-69120 Heidelberg, Germany
2
University Clinics of Heidelberg, D-69120 Heidelberg, Germany
3
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, D-52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4034; https://doi.org/10.3390/ijms20164034
Received: 6 July 2019 / Revised: 15 August 2019 / Accepted: 16 August 2019 / Published: 19 August 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Phosphatidylcholine (PC) translocation into mucus of the intestine was shown to occur via a paracellular transport across the apical/lateral tight junction (TJ) barrier. In case this could also be operative in biliary epithelial cells, this may have implication for the pathogenesis of primary sclerosing cholangitis (PSC). We here evaluated the transport of PC across polarized cholangiocytes. Therefore, the biliary tumor cell line Mz-ChA-1 was grown to confluency. In transwell culture systems the translocation of PC to the apical compartment was analyzed. After 21 days in culture, polarized Mz-ChA-1 cells revealed a predominant apical translocation of choline containing phospholipids including PC with minimal intracellular accumulation. Transport was suppressed by TJ destruction employing chemical inhibitors and pretreatment with siRNA to TJ forming proteins as well as the apical transmembrane mucin 3 as PC acceptor. Apical translocation was dependent on a negative apical electrical potential created by the cystic fibrosis transmembrane conductance regulator (CFTR) and the anion exchange protein 2 (AE2). It was stimulated by apical application of secretory mucins. The results indicated the existence of a paracellular PC passage across apical/lateral TJ of the polarized biliary epithelial tumor cell line Mz-ChA-1. This has implication for the generation of a protective mucus barrier in the biliary tree.
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Keywords:
Mz-ChA-1 cells; biliary epithelial cells; phosphatidylcholine; mucus; tight junctions; paracellular transport
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MDPI and ACS Style
Stremmel, W.; Staffer, S.; Weiskirchen, R. Phosphatidylcholine Passes by Paracellular Transport to the Apical Side of the Polarized Biliary Tumor Cell Line Mz-ChA-1. Int. J. Mol. Sci. 2019, 20, 4034.
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