• Nem Talált Eredményt

Proost N, Viveen MC, Lyubimova Teeven L, Derakhshan S, Korving J, Begthel H, 621

AUTHORS CONTRIBUTION STATEMENT 486

A, Proost N, Viveen MC, Lyubimova Teeven L, Derakhshan S, Korving J, Begthel H, 621

Dekkers JF, Kumawat K, Ramos E, van Oosterhout MF, Offerhaus GJ, Wiener DJ, 622 

Olimpio EP, Dijkstra KK, Smit EF, van der Linden M, Jaksani S, van de Ven M, 623 

Jonkers J, Rios AC, Voest EE, van Moorsel CH, van der Ent CK, Cuppen E, van 624 

Oudenaarden A, Coenjaerts FE, Meyaard L, Bont LJ, Peters PJ, Tans SJ, van Zon JS, 625 

Boj SF, Vries RG, Beekman JM, and Clevers H. Long-term expanding human airway 626 

organoids for disease modeling. EMBO J 38: 2019.

627 

6. DeWard AD, Cramer J, and Lagasse E. Cellular heterogeneity in the mouse 628 

esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 629 

9: 701-711, 2014.

630 

7. Kalabis J, Oyama K, Okawa T, Nakagawa H, Michaylira CZ, Stairs DB, 631 

Figueiredo JL, Mahmood U, Diehl JA, Herlyn M, and Rustgi AK. A subpopulation of 632 

mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal 633 

and lineage specification. J Clin Invest 118: 3860-3869, 2008.

634 

8. Thomas JA, Buchsbaum RN, Zimniak A, and Racker E. Intracellular pH 635 

measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ.

636 

Biochemistry 18: 2210-2218, 1979.

637 

9. Hegyi P, Rakonczay Z, Jr., Gray MA, and Argent BE. Measurement of 638 

intracellular pH in pancreatic duct cells: a new method for calibrating the fluorescence data.

639 

Pancreas 28: 427-434, 2004.

640 

10. Hegyi P, Gray MA, and Argent BE. Substance P inhibits bicarbonate secretion from 641 

guinea pig pancreatic ducts by modulating an anion exchanger. American journal of 642 

physiology Cell physiology 285: C268-276, 2003.

643 

11. Venglovecz V, Rakonczay Z, Jr., Ozsvari B, Takacs T, Lonovics J, Varro A, Gray 644 

MA, Argent BE, and Hegyi P. Effects of bile acids on pancreatic ductal bicarbonate 645 

secretion in guinea pig. Gut 57: 1102-1112, 2008.

646 

12. Harnden P, and Southgate J. Cytokeratin 14 as a marker of squamous differentiation 647 

in transitional cell carcinomas. J Clin Pathol 50: 1032-1033, 1997.

648 

13. Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, and Schmitt FC.

649 

Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic 650 

human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443: 122-651 

132, 2003.

652 

14. Fong P. CFTR-SLC26 transporter interactions in epithelia. Biophys Rev 4: 107-116, 653 

2012.

654 

15. Weintraub WH, and Machen TE. pH regulation in hepatoma cells: roles for Na-H 655 

exchange, Cl-HCO3 exchange, and Na-HCO3 cotransport. The American journal of 656 

physiology 257: G317-327, 1989.

657 

16. Slepkov ER, Rainey JK, Sykes BD, and Fliegel L. Structural and functional analysis 658 

of the Na+/H+ exchanger. Biochem J 401: 623-633, 2007.

659 

17. Pallagi-Kunstar E, Farkas K, Maleth J, Rakonczay Z, Jr., Nagy F, Molnar T, 660 

Szepes Z, Venglovecz V, Lonovics J, Razga Z, Wittmann T, and Hegyi P. Bile acids 661 

inhibit Na(+)/H(+) exchanger and Cl(-)/HCO(3)(-) exchanger activities via cellular energy 662 

breakdown and Ca(2)(+) overload in human colonic crypts. Pflugers Arch 467: 1277-1290, 663 

2015.

664 

18. Venglovecz V, Hegyi P, Rakonczay Z, Jr., Tiszlavicz L, Nardi A, Grunnet M, and 665 

Gray MA. Pathophysiological relevance of apical large-conductance Ca(2)+-activated 666 

potassium channels in pancreatic duct epithelial cells. Gut 60: 361-369, 2011.

667 

19. Tobey NA, Koves G, and Orlando RC. Human esophageal epithelial cells possess an 668 

Na+/H+ exchanger for H+ extrusion. Am J Gastroenterol 93: 2075-2081, 1998.

669 

20. Tobey NA, Reddy SP, Keku TO, Cragoe EJ, Jr., and Orlando RC. Studies of pHi 670 

in rabbit esophageal basal and squamous epithelial cells in culture. Gastroenterology 103:

671 

830-839, 1992.

672 

21. Shallat S, Schmidt L, Reaka A, Rao D, Chang EB, Rao MC, Ramaswamy K, and 673 

Layden TJ. NHE-1 isoform of the Na+/H+ antiport is expressed in the rat and rabbit 674 

esophagus. Gastroenterology 109: 1421-1428, 1995.

675 

22. Ariyoshi Y, Shiozaki A, Ichikawa D, Shimizu H, Kosuga T, Konishi H, Komatsu 676 

S, Fujiwara H, Okamoto K, Kishimoto M, Marunaka Y, and Otsuji E. Na+/H+

677 

exchanger 1 has tumor suppressive activity and prognostic value in esophageal squamous cell 678 

carcinoma. Oncotarget 8: 2209-2223, 2017.

679 

23. Guan B, Hoque A, and Xu X. Amiloride and guggulsterone suppression of 680 

esophageal cancer cell growth in vitro and in nude mouse xenografts. Front Biol (Beijing) 9:

681 

75-81, 2014.

682 

24. Yang SC, Chen CL, Yi CH, Liu TT, and Shieh KR. Changes in Gene Expression 683 

Patterns of Circadian-Clock, Transient Receptor Potential Vanilloid-1 and Nerve Growth 684 

Factor in Inflamed Human Esophagus. Sci Rep 5: 13602, 2015.

685 

25. Zeng C, Vanoni S, Wu D, Caldwell JM, Wheeler JC, Arora K, Noah TK, 686 

Waggoner L, Besse JA, Yamani AN, Uddin J, Rochman M, Wen T, Chehade M, Collins 687 

MH, Mukkada VA, Putnam PE, Naren AP, Rothenberg ME, and Hogan SP. Solute 688 

carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 689 

(NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic 690 

esophagitis. J Allergy Clin Immunol 142: 1843-1855, 2018.

691 

26. Abdulnour-Nakhoul S, Nakhoul HN, Kalliny MI, Gyftopoulos A, Rabon E, 692 

Doetjes R, Brown K, and Nakhoul NL. Ion transport mechanisms linked to bicarbonate 693 

secretion in the esophageal submucosal glands. Am J Physiol Regul Integr Comp Physiol 301:

694 

R83-96, 2011.

695 

27. Abdulnour-Nakhoul S, Nakhoul NL, Wheeler SA, Wang P, Swenson ER, and 696 

Orlando RC. HCO3- secretion in the esophageal submucosal glands. Am J Physiol 697 

Gastrointest Liver Physiol 288: G736-744, 2005.

698 

28. Tobey NA, Reddy SP, Khalbuss WE, Silvers SM, Cragoe EJ, Jr., and Orlando 699 

RC. Na(+)-dependent and -independent Cl-/HCO3- exchangers in cultured rabbit esophageal 700 

epithelial cells. Gastroenterology 104: 185-195, 1993.

701 

29. Wang J, Wang W, Wang H, and Tuo B. Physiological and Pathological Functions 702 

of SLC26A6. Front Med (Lausanne) 7: 618256, 2020.

703 

30. Ko SB, Zeng W, Dorwart MR, Luo X, Kim KH, Millen L, Goto H, Naruse S, 704 

Soyombo A, Thomas PJ, and Muallem S. Gating of CFTR by the STAS domain of SLC26 705 

transporters. Nat Cell Biol 6: 343-350, 2004.

706 

31. Stewart AK, Yamamoto A, Nakakuki M, Kondo T, Alper SL, and Ishiguro H.

707 

Functional coupling of apical Cl-/HCO3- exchange with CFTR in stimulated HCO3- secretion 708 

by guinea pig interlobular pancreatic duct. Am J Physiol Gastrointest Liver Physiol 296:

709 

G1307-1317, 2009.

710 

32. Saint-Criq V, and Gray MA. Role of CFTR in epithelial physiology. Cell Mol Life 711 

Sci 74: 93-115, 2017.

712 

33. Kruger L, Pridgen TA, Taylor ER, Garman KS, and Blikslager AT. Lubiprostone 713 

protects esophageal mucosa from acid injury in porcine esophagus. Am J Physiol Gastrointest 714 

Liver Physiol 318: G613-G623, 2020.

715 

34. Ao M, Venkatasubramanian J, Boonkaewwan C, Ganesan N, Syed A, Benya RV, 716 

and Rao MC. Lubiprostone activates Cl- secretion via cAMP signaling and increases 717 

membrane CFTR in the human colon carcinoma cell line, T84. Dig Dis Sci 56: 339-351, 718 

2011.

719 

35. Norimatsu Y, Moran AR, and MacDonald KD. Lubiprostone activates CFTR, but 720 

not ClC-2, via the prostaglandin receptor (EP(4)). Biochem Biophys Res Commun 426: 374-721 

379, 2012.

722 

36. Gharahkhani P, Fitzgerald RC, Vaughan TL, Palles C, Gockel I, Tomlinson I, 723 

Buas MF, May A, Gerges C, Anders M, Becker J, Kreuser N, Noder T, Venerito M, 724 

Veits L, Schmidt T, Manner H, Schmidt C, Hess T, Bohmer AC, Izbicki JR, Holscher 725 

AH, Lang H, Lorenz D, Schumacher B, Hackelsberger A, Mayershofer R, Pech O, 726 

Vashist Y, Ott K, Vieth M, Weismuller J, Nothen MM, Barrett's, Esophageal 727 

Adenocarcinoma C, Esophageal Adenocarcinoma GenEtics C, Wellcome Trust Case 728 

Control C, Attwood S, Barr H, Chegwidden L, de Caestecker J, Harrison R, Love SB, 729 

MacDonald D, Moayyedi P, Prenen H, Watson RGP, Iyer PG, Anderson LA, Bernstein 730 

L, Chow WH, Hardie LJ, Lagergren J, Liu G, Risch HA, Wu AH, Ye W, Bird NC, 731 

Shaheen NJ, Gammon MD, Corley DA, Caldas C, Moebus S, Knapp M, Peters WHM, 732 

Neuhaus H, Rosch T, Ell C, MacGregor S, Pharoah P, Whiteman DC, Jankowski J, and 733 

Schumacher J. Genome-wide association studies in oesophageal adenocarcinoma and 734 

Barrett's oesophagus: a large-scale meta-analysis. Lancet Oncol 17: 1363-1373, 2016.

735 

37. Hassall E, Israel DM, Davidson AG, and Wong LT. Barrett's esophagus in children 736 

with cystic fibrosis: not a coincidental association. Am J Gastroenterol 88: 1934-1938, 1993.

737 

38. Holt EW, Yimam KK, and Liberman MS. Esophageal adenocarcinoma in a 40-738 

year-old man with cystic fibrosis: coincidence or not? Ochsner J 13: 252-255, 2013.

739 

39. Li W, Wang C, Peng X, Zhang H, Huang H, and Liu H. CFTR inhibits the invasion 740 

and growth of esophageal cancer cells by inhibiting the expression of NF-kappaB. Cell Biol 741 

Int 42: 1680-1687, 2018.

742 

40. Matsumoto Y, Shiozaki A, Kosuga T, Kudou M, Shimizu H, Arita T, Konishi H, 743 

Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, and Otsuji E.

744 

Expression and Role of CFTR in Human Esophageal Squamous Cell Carcinoma. Ann Surg 745 

Oncol 2021.

746 

41. Vanoni S, Zeng C, Marella S, Uddin J, Wu D, Arora K, Ptaschinski C, Que J, 747 

Noah T, Waggoner L, Barski A, Kartashov A, Rochman M, Wen T, Martin L, Spence J, 748 

Collins M, Mukkada V, Putnam P, Naren A, Chehade M, Rothenberg ME, and Hogan 749 

SP. Identification of anoctamin 1 (ANO1) as a key driver of esophageal epithelial 750 

proliferation in eosinophilic esophagitis. J Allergy Clin Immunol 145: 239-254 e232, 2020.

751 

752 

Figure 1

A B

C

Days after plating

3 5 7 9

C57Bl/6CD-1

A

Percentage of LGR5 positive cells (%)

CD-1 C57Bl/6

B

Percentage of CK14 positive cells (%)

C

Percentage of LGR5+CK14+ positive cells (%)

CD-1

Figure 3

A B C

M Slc9a1 Slc9a2 Slc26a6 CFTR Slc4a4 M Slc26a3 ANO1 O K O K O K O K O K O P O P

M Slc9a1 Slc9a2 Slc26a6 CFTR Slc4a4 M Slc26a3 ANO1

C57BL/6

CD-1

O K O K O K O K O K O P O P

Figure 4

B C

6.50 7.00 7.50 8.00 8.50

pHi

Na+-free

Hepes

NH4Cl NH4Cl NH4Cl NH4Cl 20 5 15 10 25 5 20 15 25 10

100 150 200 250 300 350 400

ering capacity (mM/pHU)

ßHCO3 i

ßtotal 3.0

4.0 5.0 6.0 7.0 8.0

440/495

3 min 3.0

4.0 5.0 6.0 7.0 8.0

440/495

Hepes

7.2 7.4 7.6 7.2 7.4 7.6

3 min

Hepes

7.2 7.4 7.6 7.2 7.4 7.6

A

Figure 5

Figure 6

Hepes

6.0 6.5 7.0 7.5 8.0 8.5

pH

i

6.0 6.5 7.0 7.5 8.0 8.5

pH

i

Hepes

Na+-free

NH4Cl NH4Cl Na+-free NH4Cl Na+-free

1 µM HOE-642 50 µM HOE-642

Na+-free

NH4Cl NH4Cl Na+-free NH4Cl Na+-free

1 µM HOE-642 50 µM HOE-642

3 min 3 min

B A

Hepes

100 150 200 250 300

J(B-)

C57BL/6 CD-1

Figure 7

B A

6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2

pH

i

6.6 6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2

pH

i