Evidence map›Paper›PMID 34326316›Full record

ArticleCell death discovery2021

Probing tissue transglutaminase mediated vascular smooth muscle cell aging using a novel transamidation-deficient Tgm2-C277S mouse model.

Huilei Wang, James Chen, Sandeep Jandu, Sean Melucci, William Savage, Kavitha Nandakumar, Sara K Kang, Sebastian Barreto-Ortiz, Alan Poe, Shivam Rastogi and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Sex differences and role of lysyl oxidase-like 2 in angiotensin II-induced hypertension in mice.American journal of physiology. Heart and circulatory physiology · 2024
    Article
  5. Article
  6. Article
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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

13 authors at 1 institution in 1 country.

Huilei Wang *Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-6979-9509
James Chen *Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-5053-6151
Sandeep Jandu *Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sean Melucci *Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
William Savage *Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Kavitha Nandakumar *Department of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sara K KangDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sebastian Barreto-OrtizDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Alan PoeDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Shivam RastogiDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Maria BauerDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Jochen SteppanDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Lakshmi SanthanamDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. LSantha1@jhmi.edu.
Johns Hopkins University · US

Funding

Lysyl Oxidase Like 2: A Novel Target in Aging Associated Vascular StiffeningR01HL148112 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SANTHANAM, LAKSHMI · 2020 to 2023
$1.9M
The Therapeutic Role for LOLX2 in Pulmonary HypertensionK08HL145132 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI STEPPAN, JOCHEN · 2019 to 2023
$859k
NHLBI NIH HHS K08 HL145132U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL148112
6 · The paper itself

Abstract

Tissue transglutaminase (TG2), a multifunctional protein of the transglutaminase family, has putative transamidation-independent functions in aging-associated vascular stiffening and dysfunction. Developing preclinical models will be critical to fully understand the physiologic relevance of TG2's transamidation-independent activity and to identify the specific function of TG2 for therapeutic targeting. Therefore, in this study, we harnessed CRISPR-Cas9 gene editing technology to introduce a mutation at cysteine 277 in the active site of the mouse Tgm2 gene. Heterozygous and homozygous Tgm2-C277S mice were phenotypically normal and were born at the expected Mendelian frequency. TG2 protein was ubiquitously expressed in the Tgm2-C277S mice at levels similar to those of wild-type (WT) mice. In the Tgm2-C277S mice, TG2 transglutaminase function was successfully obliterated, but the transamidation-independent functions ascribed to GTP, fibronectin, and integrin binding were preserved. In vitro, a remodeling stimulus led to the significant loss of vascular compliance in WT mice, but not in the Tgm2-C277S or TG2

Identifiers

PMID34326316
PMCPMC8322091
OpenAlexW3185993915

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LicenceCC BY
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Registered trials

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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.