Evidence map›Paper›PMID 26443820›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Basement membrane stiffening promotes retinal endothelial activation associated with diabetes.

Xiao Yang, Harry A Scott, Finny Monickaraj, Jun Xu, Soroush Ardekani, Carolina F Nitta, Andrea Cabrera, Paul G McGuire, Umar Mohideen, Arup Das and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Basement membrane structure and function: Relating biology to mechanics.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  3. IGF-II regulates lysyl oxidase propeptide and mediates its effects in part via basic helix-loop-helix E40.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Implications of fibrotic extracellular matrix in diabetic retinopathy.Experimental biology and medicine (Maywood, N.J.) · 2022
    Review
  12. Article
  13. Directing Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Role of the lysyl oxidase family in organ development (Review).Experimental and therapeutic medicine · 2020
    Review
  20. 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

11 authors at 3 institutions in 1 country.

Xiao Yang*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Harry A Scott*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Finny Monickaraj*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Jun Xu*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Soroush Ardekani*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Carolina F Nitta*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Andrea Cabrera*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Paul G McGuire*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Umar Mohideen*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Arup Das*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA.
Kaustabh Ghosh*Department of Bioengineering and Department of Physics and Astronomy, University of California, Riverside, Riverside, California, USA; Department of Surgery and Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico, USA; and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico, USA kghosh@engr.ucr.edu.
University of California, Riverside · USUniversity of New Mexico · USNew Mexico VA Health Care System · US

Funding

Inflammatory Chemokines: A Novel Target in Early Diabetic RetinopathyR01EY022327 · NEI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI DAS, ARUP · 2013 to 2015
$1.1M
NEI NIH HHS R01 EY022327NEI NIH HHS R01EY022327
6 · The paper itself

Abstract

Endothelial activation is a hallmark of the high-glucose (HG)-induced retinal inflammation associated with diabetic retinopathy (DR). However, precisely how HG induces retinal endothelial activation is not fully understood. We hypothesized that HG-induced up-regulation of lysyl oxidase (LOX), a collagen-cross-linking enzyme, in retinal capillary endothelial cells (ECs) enhances subendothelial basement membrane (BM) stiffness, which, in turn, promotes retinal EC activation. Diabetic C57BL/6 mice exhibiting a 70 and 50% increase in retinal intercellular adhesion molecule (ICAM)-1 expression and leukocyte accumulation, respectively, demonstrated a 2-fold increase in the levels of BM collagen IV and LOX, key determinants of capillary BM stiffness. Using atomic force microscopy, we confirmed that HG significantly enhances LOX-dependent subendothelial matrix stiffness in vitro, which correlated with an ∼2.5-fold increase in endothelial ICAM-1 expression, a 4-fold greater monocyte-EC adhesion, and an ∼2-fold alteration in endothelial NO (decrease) and NF-κB activation (increase). Inhibition of LOX-dependent subendothelial matrix stiffening alone suppressed HG-induced retinal EC activation. Finally, using synthetic matrices of tunable stiffness, we demonstrated that subendothelial matrix stiffening is necessary and sufficient to promote EC activation. These findings implicate BM stiffening as a critical determinant of HG-induced retinal EC activation and provide a rationale for examining BM stiffness and underlying mechanotransduction pathways as therapeutic targets for diabetic retinopathy.

Indexed as

AnimalsBasement MembraneCell LineDiabetes Mellitus, ExperimentalDiabetic RetinopathyEndothelial CellsEndotheliumGene Expression RegulationHaplorhiniHumansMiceMice, Inbred C57BLMonocytesProtein-Lysine 6-OxidaseRetinaProtein-Lysine 6-Oxidasediabetic retinopathyinflammationlysyl oxidasematrix stiffnessnitric oxide

Identifiers

PMID26443820
PMCPMC6188223
OpenAlexW2273156803

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.