Evidence map›Paper›PMID 30759273›Full record

ArticleLung2019

Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome.

Chintan K Gandhi, Romel Holmes, Ira H Gewolb, Bruce D Uhal

Open access · bronzeAbstract read
In one paragraph

Article in Lung, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Review
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

4 authors at 2 institutions in 2 countries.

Chintan K GandhiDivision of Neonatology, Department of Pediatrics & Human Development, Michigan State University, East Lansing, MI, USA.
Romel HolmesBiology, Tuskegee University, Tuskegee, AL, USA.
Ira H GewolbDivision of Neonatology, Department of Pediatrics & Human Development, Michigan State University, East Lansing, MI, USA.
Bruce D UhalDepartment of Physiology, Michigan State University, 3197 Biomedical and Physical Sciences Building, East Lansing, MI, 48824, USA. uhal@msu.edu.
Michigan State University · USTuskegee University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before.

objectiveTo study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2.

methodsAlveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity.

resultsMeconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05).

conclusionThese data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.

Indexed as

A549 CellsAngiotensin-Converting Enzyme 2ApoptosisEnzyme StabilityEpithelial CellsHumansMeconiumMeconium Aspiration SyndromePeptide HydrolasesPeptidyl-Dipeptidase AProteolysisPulmonary AlveoliACE2 protein, humanAngiotensin-Converting Enzyme 2Peptide HydrolasesPeptidyl-Dipeptidase AAngiotensin-converting enzyme 2Meconium aspiration syndromeNeonatal lung injuryRenin-angiotensin system

Identifiers

PMID30759273
PMCPMC7088148
OpenAlexW2913227462

What OpenQuestion holds

Textmetadata
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.