Evidence map›Paper›PMID 27106638›Full record

ArticleJournal of the American College of Surgeons2016

Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels.

Wei Liu, Dong Hu, Haizhong Huo, Weifeng Zhang, Fatemeh Adiliaghdam, Sarah Morrison, Juan M Ramirez, Sarah S Gul, Sulaiman R Hamarneh, Richard A Hodin

Abstract read
In one paragraph

Article in Journal of the American College of Surgeons, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.5field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 124 citations in OpenAlex.

  1. Trial
  2. Review
  3. The Relationship Between Obesity and Intestinal Alkaline Phosphatase: A Clinical and Biochemical Study.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026
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  17. Alkaline phosphatase treatment of acute kidney injury-an update.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
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  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Wei LiuDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Dong HuDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Haizhong HuoDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Weifeng ZhangDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Fatemeh AdiliaghdamDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Sarah MorrisonDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Juan M RamirezDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Sarah S GulDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Sulaiman R HamarnehDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Richard A HodinDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Electronic address: rhodin@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
RESEARCH TRAINING IN ALIMENTARY TRACT SURGERYT32DK007754 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HODIN, RICHARD A. · 1997 to 2025
$6.5M
NIDDK NIH HHS P30 DK043351NIDDK NIH HHS T32 DK007754
6 · The paper itself

Abstract

backgroundIntestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. STUDY

designThe effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER).

resultsIntestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP overexpression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function.

conclusionsIntestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function.

Indexed as

Alkaline PhosphataseAnimalsBiomarkersBlotting, WesternCaco-2 CellsDown-RegulationElectric ImpedanceFibroblastsFluorescent Antibody TechniqueHumansIntestinal MucosaMiceMice, KnockoutPermeabilityReal-Time Polymerase Chain ReactionTight JunctionsAlkaline PhosphataseBiomarkers

Identifiers

PMID27106638
PMCPMC5684582
OpenAlexW2205155415

What OpenQuestion holds

Textmetadata
LicenceTDM
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.