Evidence map›Paper›PMID 21372207›Full record

ArticleJournal of the American Society of Nephrology : JASN2011

Type VIII collagen modulates TGF-β1-induced proliferation of mesangial cells.

Ivonne Loeffler, Ulrike Hopfer, Dirk Koczan, Gunter Wolf

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Type VIII collagen: advances in matrix biology and translational promise.Frontiers in bioengineering and biotechnology · 2025
    Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Collagen VIII in vascular diseases.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Review
  8. Article
  9. The Role of Collagen VIII in the Aging Mouse Kidney.International journal of molecular sciences · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. COL8A2 Regulates the Fate of Corneal Endothelial Cells.Investigative ophthalmology & visual science · 2020
    Article
  20. Article
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 3 institutions in 2 countries.

Ivonne LoefflerDepartment of Internal Medicine III, University of Jena, Erlanger Allee 101, D-07740 Jena, Germany.
Ulrike Hopfer
Dirk Koczan
Gunter Wolf
Friedrich Schiller University Jena · DEUniversity of Basel · CHUniversity of Rostock · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesangial cells in diabetic mice and human kidneys with diabetic nephropathy exhibit increased type VIII collagen, a nonfibrillar protein that exists as a heterodimer composed of α1(VIII) and α2(VIII), encoded by Col8a1 and Col8a2, respectively. Because TGF-β1 promotes the development of diabetic glomerulosclerosis, we studied whether type VIII collagen modulates the effects of TGF-β1 in mesangial cells. We obtained primary cultures of mesangial cells from wild-type, doubly heterozygous (Col8a1(+/-)/Col8a2(+/-)), and double-knockout (Col8a1(-/-)/Col8a2(-/-)) mice. TGF-β1 bound normally to double-knockout mesangial cells. In wild-type mesangial cells, TGF-β1 inhibited proliferation, but in double-knockout cells, it stimulated proliferation, promoted cell cycle progression, and reduced apoptosis; we could reverse this effect by reconstituting α1(VIII). Furthermore, in wild-type cells, TGF-β1 mainly stimulated the Smad pathways, whereas in double-knockout cells, it activated the MAPK and PI3K/Akt pathways and induced expression of fibroblast growth factor 21 (FGF21). Inhibiting FGF21 expression by either interfering with activation of the MAPK and PI3K/Akt pathways or by FGF21 siRNA attenuated the TGF-β1-induced proliferation of double-knockout mesangial cells. In vivo, diabetic double-knockout mice had significantly higher expression of renal FGF21 mRNA and protein compared with diabetic wild-type mice. Immunohistochemistry revealed strong expression of FGF21 in both glomerular (mesangial) and tubular cells of diabetic mice. Taken together, these data suggest that type VIII collagen significantly modulates the effect of TGF-β1 on mesangial cells and may therefore play a role in the pathogenesis of diabetic nephropathy.

Indexed as

AnimalsApoptosisCell CycleCell ProliferationCells, CulturedCollagen Type VIIIDiabetes Mellitus, ExperimentalDiabetic NephropathiesDisease Models, AnimalFibroblast Growth FactorsMesangial CellsMiceMice, KnockoutMitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesStreptozocinCollagen Type VIIIfibroblast growth factor 21Fibroblast Growth FactorsMitogen-Activated Protein Kinase KinasesPhosphatidylinositol 3-KinasesStreptozocinTransforming Growth Factor beta1

Identifiers

PMID21372207
PMCPMC3065221
OpenAlexW2099507049

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.