Evidence map›Paper›PMID 28090569›Full record

ArticleCellular and molecular gastroenterology and hepatology2017

Mitogen-activated Protein Kinase Kinase Activity Maintains Acinar-to-Ductal Metaplasia and Is Required for Organ Regeneration in Pancreatitis.

Christopher J Halbrook, Hui-Ju Wen, Jeanine M Ruggeri, Kenneth K Takeuchi, Yaqing Zhang, Marina Pasca di Magliano, Howard C Crawford

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.9field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 63 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Christopher J HalbrookDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Hui-Ju WenDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Jeanine M RuggeriDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Kenneth K TakeuchiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Yaqing ZhangDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Marina Pasca di MaglianoDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Howard C CrawfordDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
University of Michigan–Ann Arbor · US

Funding

Mechanisms of Pancreatic Inflammation, Tissue Repair and CarcinogenesisR01CA151588 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA · 2010 to 2020
$3.3M
ADAM17 in pancreatic cancer and pancreatitisR01CA159222 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C. · 2011 to 2015
$1.9M
Dosage-Dependent Hedgehog Signaling in Pancreatic CancerR01CA198074 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN, PASCA DI MAGLIANO, MARINA · 2015 to 2019
$1.9M
NCI NIH HHS R01 CA151588NCI NIH HHS R01 CA159222NCI NIH HHS R01 CA198074
6 · The paper itself

Abstract

BACKGROUND &

aimsMitogen-activated protein kinase (MAPK) signaling in the exocrine pancreas has been extensively studied in the context of pancreatic cancer, where its potential as a therapeutic target is limited by acquired drug resistance. However, its role in pancreatitis is less understood. We investigated the role of mitogen-activated protein kinase kinase (MEK)-initiated MAPK signaling in pancreatitis to determine the potential for MEK inhibition in treating pancreatitis patients.

methodsTo examine the role of MEK signaling in pancreatitis, we used both genetic and pharmacologic approaches to inhibit the MAPK signaling pathway in a murine model of cerulein-induced pancreatitis. We generated mice harboring inducible short hairpins targeting the MEK isoforms

resultsWe demonstrated an essential role for MEK signaling in the initiation of pancreatitis. We showed that both systemic and parenchyma-specific MEK inhibition in established pancreatitis induces epithelial differentiation and stromal remodeling. However, systemic MEK inhibition also leads to a loss of the proliferative capacity of the pancreas, preventing the restoration of organ mass.

conclusionsMEK activity is required for the initiation and maintenance of pancreatitis. MEK inhibition may be useful in the treatment of chronic pancreatitis to interrupt the vicious cycle of destruction and repair but at the expense of organ regeneration.

Indexed as

ADMInflammationTissue RegenerationWound Healing

Identifiers

PMID28090569
PMCPMC5235341
OpenAlexW2529994686

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.