Evidence map›Paper›PMID 37643024›Full record

ArticleJCI insight2023

Acid-base homeostasis orchestrated by NHE1 defines the pancreatic stellate cell phenotype in pancreatic cancer.

Zoltán Pethő, Karolina Najder, Stephanie Beel, Benedikt Fels, Ilka Neumann, Sandra Schimmelpfennig, Sarah Sargin, Maria Wolters, Klavs Grantins, Eva Wardelmann and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Discovery of vasodilatory effects of NaActa pharmacologica Sinica · 2026
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  2. TRPV6-Mediated CaCancers · 2026
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  3. Review
  4. Article
  5. Review
  6. Article
  7. KPflugers Archiv : European journal of physiology · 2025
    Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Zoltán PethőInstitute of Physiology II and.
Karolina NajderInstitute of Physiology II and.
Stephanie BeelInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Benedikt FelsInstitute of Physiology II and.
Ilka NeumannInstitute of Physiology II and.
Sandra SchimmelpfennigInstitute of Physiology II and.
Sarah SarginInstitute of Physiology II and.
Maria WoltersGerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
Klavs GrantinsGerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
Eva WardelmannGerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.
Miso MitkovskiCity Campus Light Microscopy Facility, Max Planck Institute for Multidisciplinary Sciences, Goettingen, Germany.
Andrea OeckinghausInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Albrecht SchwabInstitute of Physiology II and.
University of Münster · DECzech Academy of Sciences, Institute of Physiology · CZMax Planck Institute for Multidisciplinary Sciences

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) progresses in an organ with a unique pH landscape, where the stroma acidifies after each meal. We hypothesized that disrupting this pH landscape during PDAC progression triggers pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) to induce PDAC fibrosis. We revealed that alkaline environmental pH was sufficient to induce PSC differentiation to a myofibroblastic phenotype. We then mechanistically dissected this finding, focusing on the involvement of the Na+/H+ exchanger NHE1. Perturbing cellular pH homeostasis by inhibiting NHE1 with cariporide partially altered the myofibroblastic PSC phenotype. To show the relevance of this finding in vivo, we targeted NHE1 in murine PDAC (KPfC). Indeed, tumor fibrosis decreased when mice received the NHE1-inhibitor cariporide in addition to gemcitabine treatment. Moreover, the tumor immune infiltrate shifted from granulocyte rich to more lymphocytic. Taken together, our study provides mechanistic evidence on how the pancreatic pH landscape shapes pancreatic cancer through tuning PSC differentiation.

Indexed as

Carcinoma, Pancreatic DuctalPancreatic NeoplasmsAnimalsCell Line, TumorFibrosisGuanidinesHomeostasisMicePancreatic Stellate CellsPhenotypeSulfonescariporideGuanidinesSulfonesEpithelial transport of ions and waterFibrosisHomeostasisMetabolismOncology

Identifiers

PMID37643024
PMCPMC10619433
OpenAlexW4386257118

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.