Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Autorschaft

  • Katerina Nikolovska
  • Li Cao
  • Inga Hensel
  • Gabriella Di Stefano
  • Anna Elisabeth Seidler
  • Kunyan Zhou
  • Jiajie Qian
  • Anurag Kumar Singh
  • Brigitte Riederer
  • Ursula Seidler

Externe Organisationen

  • Medizinische Hochschule Hannover (MHH)
  • Huazhong University of Science and Technology
  • Zhejiang University (ZJU)
  • Martin-Luther-Universität Halle-Wittenberg
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Aufsatznummere13774
FachzeitschriftActa Physiologica
Jahrgang234
Ausgabenummer3
PublikationsstatusVeröffentlicht - 5 Jan. 2022
Extern publiziertJa

Abstract

Aim: The sodium/hydrogen exchanger 2 (NHE2) is an intestinal acid extruder with crypt-predominant localization and unresolved physiological significance. Our aim was to decipher its role in colonic epithelial cell proliferation, differentiation and electrolyte transport. Methods: Alterations induced by NHE2-deficiency were addressed in murine nhe2−/− and nhe2+/+ colonic crypts and colonoids, and NHE2-knockdown and control Caco2Bbe cells using pH-fluorometry, gene expression analysis and immunofluorescence. Results: pHi-measurements along the colonic cryptal axis revealed significantly decreased intracellular pH (pHi) in the middle segment of nhe2−/− compared to nhe2+/+ crypts. Increased Nhe2 mRNA expression was detected in murine colonoids in the transiently amplifying/progenitor cell stage (TA/PE). Lack of Nhe2 altered the differentiation programme of colonic epithelial cells with reduced expression of absorptive lineage markers alkaline phosphatase (iAlp), Slc26a3 and transcription factor hairy and enhancer-of-split 1 (Hes1), but increased expression of secretory lineage markers Mucin 2, trefoil factor 3 (Tff3), enteroendocrine marker chromogranin A and murine atonal homolog 1 (Math1). Enterocyte differentiation was found to be pHi dependent with acidic pHi reducing, and alkaline pHi stimulating the expression of enterocyte differentiation markers in Caco2Bbe cells. A thicker mucus layer, longer crypts and an expanded brush border membrane zone of sodium/hydrogen exchanger 3 (NHE3) abundance may explain the lack of inflammation and the normal fluid absorptive rate in nhe2−/− colon. Conclusions: The results suggest that NHE2 expression is activated when colonocytes emerge from the stem cell niche. Its activity increases progenitor cell pHi and thereby supports absorptive enterocyte differentiation.

ASJC Scopus Sachgebiete

  • Biochemie, Genetik und Molekularbiologie (insg.)
  • Physiologie

Zitieren

Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation. / Nikolovska, Katerina; Cao, Li; Hensel, Inga et al.
in: Acta Physiologica, Jahrgang 234, Nr. 3, e13774, 05.01.2022.

Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review

Nikolovska, K, Cao, L, Hensel, I, Di Stefano, G, Seidler, AE, Zhou, K, Qian, J, Singh, AK, Riederer, B & Seidler, U 2022, 'Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation', Acta Physiologica, Jg. 234, Nr. 3, e13774. https://doi.org/10.1111/apha.13774
Nikolovska, K., Cao, L., Hensel, I., Di Stefano, G., Seidler, AE., Zhou, K., Qian, J., Singh, A. K., Riederer, B., & Seidler, U. (2022). Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation. Acta Physiologica, 234(3), Artikel e13774. https://doi.org/10.1111/apha.13774
Nikolovska K, Cao L, Hensel I, Di Stefano G, Seidler AE, Zhou K et al. Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation. Acta Physiologica. 2022 Jan 5;234(3):e13774. doi: 10.1111/apha.13774
Nikolovska, Katerina ; Cao, Li ; Hensel, Inga et al. / Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation. in: Acta Physiologica. 2022 ; Jahrgang 234, Nr. 3.
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title = "Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation",
abstract = "Aim: The sodium/hydrogen exchanger 2 (NHE2) is an intestinal acid extruder with crypt-predominant localization and unresolved physiological significance. Our aim was to decipher its role in colonic epithelial cell proliferation, differentiation and electrolyte transport. Methods: Alterations induced by NHE2-deficiency were addressed in murine nhe2−/− and nhe2+/+ colonic crypts and colonoids, and NHE2-knockdown and control Caco2Bbe cells using pH-fluorometry, gene expression analysis and immunofluorescence. Results: pHi-measurements along the colonic cryptal axis revealed significantly decreased intracellular pH (pHi) in the middle segment of nhe2−/− compared to nhe2+/+ crypts. Increased Nhe2 mRNA expression was detected in murine colonoids in the transiently amplifying/progenitor cell stage (TA/PE). Lack of Nhe2 altered the differentiation programme of colonic epithelial cells with reduced expression of absorptive lineage markers alkaline phosphatase (iAlp), Slc26a3 and transcription factor hairy and enhancer-of-split 1 (Hes1), but increased expression of secretory lineage markers Mucin 2, trefoil factor 3 (Tff3), enteroendocrine marker chromogranin A and murine atonal homolog 1 (Math1). Enterocyte differentiation was found to be pHi dependent with acidic pHi reducing, and alkaline pHi stimulating the expression of enterocyte differentiation markers in Caco2Bbe cells. A thicker mucus layer, longer crypts and an expanded brush border membrane zone of sodium/hydrogen exchanger 3 (NHE3) abundance may explain the lack of inflammation and the normal fluid absorptive rate in nhe2−/− colon. Conclusions: The results suggest that NHE2 expression is activated when colonocytes emerge from the stem cell niche. Its activity increases progenitor cell pHi and thereby supports absorptive enterocyte differentiation.",
keywords = "colonoids, intestinal differentiation, intestinal electrolyte transport, NHE2, pH regulation, sodium/hydrogen exchange",
author = "Katerina Nikolovska and Li Cao and Inga Hensel and {Di Stefano}, Gabriella and Anna Elisabeth Seidler and Kunyan Zhou and Jiajie Qian and Singh, {Anurag Kumar} and Brigitte Riederer and Ursula Seidler",
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T1 - Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation

AU - Nikolovska, Katerina

AU - Cao, Li

AU - Hensel, Inga

AU - Di Stefano, Gabriella

AU - Seidler, Anna Elisabeth

AU - Zhou, Kunyan

AU - Qian, Jiajie

AU - Singh, Anurag Kumar

AU - Riederer, Brigitte

AU - Seidler, Ursula

N1 - Publisher Copyright: © 2022 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society

PY - 2022/1/5

Y1 - 2022/1/5

N2 - Aim: The sodium/hydrogen exchanger 2 (NHE2) is an intestinal acid extruder with crypt-predominant localization and unresolved physiological significance. Our aim was to decipher its role in colonic epithelial cell proliferation, differentiation and electrolyte transport. Methods: Alterations induced by NHE2-deficiency were addressed in murine nhe2−/− and nhe2+/+ colonic crypts and colonoids, and NHE2-knockdown and control Caco2Bbe cells using pH-fluorometry, gene expression analysis and immunofluorescence. Results: pHi-measurements along the colonic cryptal axis revealed significantly decreased intracellular pH (pHi) in the middle segment of nhe2−/− compared to nhe2+/+ crypts. Increased Nhe2 mRNA expression was detected in murine colonoids in the transiently amplifying/progenitor cell stage (TA/PE). Lack of Nhe2 altered the differentiation programme of colonic epithelial cells with reduced expression of absorptive lineage markers alkaline phosphatase (iAlp), Slc26a3 and transcription factor hairy and enhancer-of-split 1 (Hes1), but increased expression of secretory lineage markers Mucin 2, trefoil factor 3 (Tff3), enteroendocrine marker chromogranin A and murine atonal homolog 1 (Math1). Enterocyte differentiation was found to be pHi dependent with acidic pHi reducing, and alkaline pHi stimulating the expression of enterocyte differentiation markers in Caco2Bbe cells. A thicker mucus layer, longer crypts and an expanded brush border membrane zone of sodium/hydrogen exchanger 3 (NHE3) abundance may explain the lack of inflammation and the normal fluid absorptive rate in nhe2−/− colon. Conclusions: The results suggest that NHE2 expression is activated when colonocytes emerge from the stem cell niche. Its activity increases progenitor cell pHi and thereby supports absorptive enterocyte differentiation.

AB - Aim: The sodium/hydrogen exchanger 2 (NHE2) is an intestinal acid extruder with crypt-predominant localization and unresolved physiological significance. Our aim was to decipher its role in colonic epithelial cell proliferation, differentiation and electrolyte transport. Methods: Alterations induced by NHE2-deficiency were addressed in murine nhe2−/− and nhe2+/+ colonic crypts and colonoids, and NHE2-knockdown and control Caco2Bbe cells using pH-fluorometry, gene expression analysis and immunofluorescence. Results: pHi-measurements along the colonic cryptal axis revealed significantly decreased intracellular pH (pHi) in the middle segment of nhe2−/− compared to nhe2+/+ crypts. Increased Nhe2 mRNA expression was detected in murine colonoids in the transiently amplifying/progenitor cell stage (TA/PE). Lack of Nhe2 altered the differentiation programme of colonic epithelial cells with reduced expression of absorptive lineage markers alkaline phosphatase (iAlp), Slc26a3 and transcription factor hairy and enhancer-of-split 1 (Hes1), but increased expression of secretory lineage markers Mucin 2, trefoil factor 3 (Tff3), enteroendocrine marker chromogranin A and murine atonal homolog 1 (Math1). Enterocyte differentiation was found to be pHi dependent with acidic pHi reducing, and alkaline pHi stimulating the expression of enterocyte differentiation markers in Caco2Bbe cells. A thicker mucus layer, longer crypts and an expanded brush border membrane zone of sodium/hydrogen exchanger 3 (NHE3) abundance may explain the lack of inflammation and the normal fluid absorptive rate in nhe2−/− colon. Conclusions: The results suggest that NHE2 expression is activated when colonocytes emerge from the stem cell niche. Its activity increases progenitor cell pHi and thereby supports absorptive enterocyte differentiation.

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KW - intestinal differentiation

KW - intestinal electrolyte transport

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