Evidence map›Paper›PMID 25972450›Full record

ArticleAmerican journal of physiology. Cell physiology2015

Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac fibroblasts.

Sean Martin, Huey Lin, Chukwuemeka Ejimadu, Techung Lee

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
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  4. AAV-regulatedMolecular therapy. Nucleic acids · 2024
    Article
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  9. Article
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  14. Article
  15. Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease.International journal of biological sciences · 2020
    Review
  16. Role of Sfrps in cardiovascular disease.Therapeutic advances in chronic disease · 2020
    Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Sean MartinDepartment of Biochemistry and Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.
Huey LinDepartment of Biochemistry and Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.
Chukwuemeka EjimaduDepartment of Biochemistry and Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.
Techung LeeDepartment of Biochemistry and Department of Biomedical Engineering, University at Buffalo, Buffalo, New York chunglee@buffalo.edu.
University at Buffalo, State University of New York · US

Funding

Mesenchymal Stem Cell Therapeutics in Hibernating MyocardiumR01HL084590 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI LEE, TECHUNG · 2006 to 2010
$1.9M
NHLBI NIH HHS R01 HL-84590
6 · The paper itself

Abstract

Recent studies of myocardial infarction in secreted Frizzled-related protein 2 (sFRP2) knockout mice and our hamster heart failure therapy based on sFRP2 blockade have established sFRP2 as a key profibrotic cytokine in the heart. The failing hamster heart is marked by prominent fibrosis and calcification with elevated expression of sFRP2. Noting the involvement of tissue-nonspecific alkaline phosphatase (TNAP) in bone mineralization and vascular calcification, we determined whether sFRP2 might be an upstream regulator of TNAP. Biochemical assays revealed an approximately twofold increase in the activity of TNAP and elevated levels of inorganic phosphate (Pi) in the failing heart compared with the normal heart. Neither was this change detected in the liver or hamstring muscle nor was it associated with systemic hyperphosphatemia. TNAP was readily cloned from the hamster heart and upon overexpression increased the level of extracellular but not intracellular Pi, which is consistent with the cell surface location of the ectoenzyme. In line with the previous demonstration that sFRP2 blockade attenuated fibrosis, we show here that the therapy downregulated TNAP. This in vivo finding is corroborated by the in vitro study showing that cultured cardiac fibroblasts treated with recombinant sFRP2 protein exhibited progressive increase in the expression and activity of TNAP, which was completely abrogated by cycloheximide or tunicamycin. Induction of TNAP by sFRP2 is restricted to cardiac fibroblasts among the multiple cell types examined, and was not observed with sFRP4. The current work indicates that sFRP2 may promote cardiac fibrocalcification through coordinate activation of tolloid-like metalloproteinases and TNAP.

Indexed as

Alkaline PhosphataseAnimalsAnimals, Genetically ModifiedCells, CulturedCricetinaeFibroblastsHEK293 CellsHumansMaleMembrane ProteinsMiceMice, Inbred BALB CMyocytes, CardiacSecreted Frizzled-Related ProteinsAlkaline PhosphataseALPL protein, mouseMembrane ProteinsSecreted Frizzled-Related ProteinsSfrp2 protein, mousefibrocalcificationheart failuresFRP2TNAP

Identifiers

PMID25972450
PMCPMC4525083
OpenAlexW1835047649

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.