Evidence map›Paper›PMID 24344311›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

A unique covalent bond in basement membrane is a primordial innovation for tissue evolution.

Aaron L Fidler, Roberto M Vanacore, Sergei V Chetyrkin, Vadim K Pedchenko, Gautam Bhave, Viravuth P Yin, Cody L Stothers, Kristie Lindsey Rose, W Hayes McDonald, Travis A Clark and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
5.8field-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

76 citing papers in PubMed, 178 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  8. Article
  9. Decoding collagen's thermally induced unfolding and refolding pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Peroxidasin is required for full viability in development and for maintenance of tissue mechanics in adults.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  15. Article
  16. Identification of unique α4 chain structure and conserved antiangiogenic activity of α3NC1 type IV collagen in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2023
    Article
  17. Synthesis of Sulfilimines Enabled by Copper-CatalyzedJournal of the American Chemical Society · 2023
    Article
  18. The origin of human epithelial tissue.Histology and histopathology · 2023
    Review
  19. Article
  20. Article

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

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

16 authors at 6 institutions in 2 countries.

Aaron L FidlerDepartment of Medicine, Division of Nephrology and Hypertension, Center for Matrix Biology, Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt-Ingram Cancer Center, Vanderbilt Technologies for Advanced Genomics, Department of Medical Education and Administration, Department of Pathology, Microbiology, and Immunology, and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
Roberto M Vanacore
Sergei V Chetyrkin
Vadim K Pedchenko
Gautam Bhave
Viravuth P Yin
Cody L Stothers
Kristie Lindsey Rose
W Hayes McDonald
Travis A Clark
Dorin-Bogdan Borza
Robert E Steele
Michael T Ivy
Aspirnauts
Julie K Hudson
Billy G Hudson
Hypertension Institute · USBreast Cancer Research Foundation · USLaboratoire de Biochimie · FRMount Desert Island Biological Laboratory · USTennessee State University · USUniversity of California, Irvine · US

Funding

The Maine Biomedical Research Network (INBRE)P20GM103423 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI Dustin Lynn Updike · 2012 to 2026
$60.0M
Understanding the role of thyroid hormone signaling during axolotl limb regenerationP20GM104318 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI DRUMMOND, IAIN A. · 2013 to 2023
$23.0M
TYPE IV COLLAGEN, LAMININS, AND INTEGRINS IN NORMAL AND DISEASED GLOMERULIP01DK065123 · NIDDK · VANDERBILT UNIVERSITY · PI HUDSON, BILLY GERALD · 2003 to 2012
$12.9M
STUDIES ON THE STRUCTURE OF BASEMENT MEMBRANESR01DK018381 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Sergey Petrovich Budko, BILLY GERALD HUDSON · 1986 to 2026
$12.4M
Undergraduate Research Internships in Pathobiology of Diabetic NephropathyR25DK096999 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BILLY GERALD HUDSON · 2012 to 2026
$1.6M
Role of Peroxidasin in Glomerular Matrix HomeostasisK08DK097306 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BHAVE, GAUTAM · 2013 to 2017
$739k
Collagen IV Assembly and TraffickingR15DK091009 · NIDDK · TENNESSEE STATE UNIVERSITY · PI IVY, MICHAEL · 2011 to 2011
$443k
The functional contribution and clinical value of ALCAM in cancer metastasisF31CA165787 · NCI · VANDERBILT UNIVERSITY · PI JONES-PARIS, CELESTIAL · 2012 to 2014
$69k
IMPACT OF HYPOXIA ON EPITHELIAL FUNCTIONF32DK009699 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI TAYLOR, CORMAC T · 1997 to 1998
–
NCI NIH HHS F31 CA165787NIDDK NIH HHS 2P01 DK065123-07NIDDK NIH HHS F32 DK009699NIDDK NIH HHS K08 DK097306NIDDK NIH HHS P01 DK065123NIDDK NIH HHS R01 DK018381NIDDK NIH HHS R01 DK18381NIDDK NIH HHS R15 DK091009NIDDK NIH HHS R15 DK091009-01NIDDK NIH HHS R25 DK09699-02NIDDK NIH HHS R25 DK096999NIGMS NIH HHS P20 GM103423NIGMS NIH HHS P20 GM104318
6 · The paper itself

Abstract

Basement membrane, a specialized ECM that underlies polarized epithelium of eumetazoans, provides signaling cues that regulate cell behavior and function in tissue genesis and homeostasis. A collagen IV scaffold, a major component, is essential for tissues and dysfunctional in several diseases. Studies of bovine and Drosophila tissues reveal that the scaffold is stabilized by sulfilimine chemical bonds (S = N) that covalently cross-link methionine and hydroxylysine residues at the interface of adjoining triple helical protomers. Peroxidasin, a heme peroxidase embedded in the basement membrane, produces hypohalous acid intermediates that oxidize methionine, forming the sulfilimine cross-link. We explored whether the sulfilimine cross-link is a fundamental requirement in the genesis and evolution of epithelial tissues by determining its occurrence and evolutionary origin in Eumetazoa and its essentiality in zebrafish development; 31 species, spanning 11 major phyla, were investigated for the occurrence of the sulfilimine cross-link by electrophoresis, MS, and multiple sequence alignment of de novo transcriptome and available genomic data for collagen IV and peroxidasin. The results show that the cross-link is conserved throughout Eumetazoa and arose at the divergence of Porifera and Cnidaria over 500 Mya. Also, peroxidasin, the enzyme that forms the bond, is evolutionarily conserved throughout Metazoa. Morpholino knockdown of peroxidasin in zebrafish revealed that the cross-link is essential for organogenesis. Collectively, our findings establish that the triad-a collagen IV scaffold with sulfilimine cross-links, peroxidasin, and hypohalous acids-is a primordial innovation of the ECM essential for organogenesis and tissue evolution.

Indexed as

Biological EvolutionAmino Acid SequenceAnimalsBasement MembraneCollagen Type IVCross-Linking ReagentsDrosophila melanogasterExtracellular MatrixExtracellular Matrix ProteinsHemeIminesMass SpectrometryMolecular Sequence DataPeptidesPeroxidasePeroxidasesCollagen Type IVCross-Linking ReagentsExtracellular Matrix ProteinsHemeIminesPeptidesPeroxidasePeroxidasesPeroxidasinsulfilimineSulfur Compounds

Identifiers

PMID24344311
PMCPMC3890831
OpenAlexW2064161657

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.