Evidence map›Paper›PMID 31071225›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2019

Fibroblast-specific plasminogen activator inhibitor-1 depletion ameliorates renal interstitial fibrosis after unilateral ureteral obstruction.

Lan Yao, M Frances Wright, Brandon C Farmer, Laura S Peterson, Amir M Khan, Jianyong Zhong, Leslie Gewin, Chuan-Ming Hao, Hai-Chun Yang, Agnes B Fogo

Abstract read
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-β1-receptor signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  12. Article
  13. Review
  14. Induction and transmission of oncogene-induced senescence.Cellular and molecular life sciences : CMLS · 2021
    Review
  15. Review
  16. Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  17. Review
  18. 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

10 authors.

Lan YaoDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
M Frances WrightDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Brandon C FarmerDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Laura S PetersonDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Amir M KhanDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Jianyong ZhongDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Leslie GewinDivision of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA.
Chuan-Ming HaoDivision of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
Hai-Chun YangDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Agnes B FogoDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.

Funding

RESOLUTION OF GLOMERULOSCLEROSISR01DK056942 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FOGO, AGNES B. · 2001 to 2021
$4.9M
TGF-beta Pathways that Protect Epithelia in Chronic Renal InjuryR01DK108968 · NIDDK · WASHINGTON UNIVERSITY · PI GEWIN, LESLIE S · 2016 to 2025
$3.7M
The Role of Fatty Acid Oxidation in Injured Kidney TubulesI01BX003425 · VA · VETERANS HEALTH ADMINISTRATION · PI Leslie S Gewin · 2018 to 2026
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BLRD VA I01 BX003425NIDDK NIH HHS R01 DK056942NIDDK NIH HHS R01 DK108968
6 · The paper itself

Abstract

backgroundPlasminogen activator inhibitor-1 (PAI-1) expression increases extracellular matrix deposition and contributes to interstitial fibrosis in the kidney after injury. While PAI-1 is ubiquitously expressed in the kidney, we hypothesized that interstitial fibrosis is strongly dependent on fibroblast-specific PAI-1 (fbPAI-1).

methodsTenascin C Cre (TNC Cre) and fbPAI-1 knockdown (KD) mice with green fluorescent protein (GFP) expressed within the TNC construct underwent unilateral ureteral obstruction and were sacrificed 10 days later.

resultsGFP+ cells in fbPAI-1 KD mice showed significantly reduced PAI-1 expression. Interstitial fibrosis, measured by Sirius red staining and collagen I western blot, was significantly decreased in fbPAI-1 KD compared with TNC Cre mice. There was no significant difference in transforming growth factor β (TGF-β) expression or its activation between the two groups. However, GFP+ cells from fbPAI-1 KD mice had lower TGF β and connective tissue growth factor (CTGF) expression. The number of fibroblasts was decreased in fbPAI-1 KD compared with TNC Cre mice, correlating with decreased alpha smooth muscle actin (α-SMA) expression and less fibroblast cell proliferation. TNC Cre mice had decreased E-cadherin, a marker of differentiated tubular epithelium, in contrast to preserved expression in fbPAI-1 KD. F4/80-expressing cells, mostly CD11c+/F4/80+ cells, were increased while M1 macrophage markers were decreased in fbPAI-1 KD compared with TNC Cre mice.

conclusionThese findings indicate that fbPAI-1 depletion ameliorates interstitial fibrosis by decreasing fibroblast proliferation in the renal interstitium, with resulting decreased collagen I. This is linked to decreased M1 macrophages and preserved tubular epithelium.

Indexed as

ActinsAnimalsCollagen Type IConnective Tissue Growth FactorExtracellular Matrix ProteinsFibroblastsFibrosisKidney DiseasesMiceMice, KnockoutNerve Tissue ProteinsSerpin E2Transforming Growth Factor betaUreteral ObstructionActa2 protein, mouseActinsCCN2 protein, mouseCollagen Type IConnective Tissue Growth FactorExtracellular Matrix ProteinsNerve Tissue ProteinsneuronectinSerpin E2Serpine2 protein, mouseTransforming Growth Factor betafibroblastinterstitial fibrosisPAI-1

Identifiers

PMID31071225
PMCPMC6887698

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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.