Evidence map›Paper›PMID 27566305›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2017

Matrix metalloproteinase 9-dependent Notch signaling contributes to kidney fibrosis through peritubular endothelial-mesenchymal transition.

Ye Zhao, Xi Qiao, Thian Kui Tan, Hong Zhao, Yun Zhang, Lixin Liu, Jianlin Zhang, Lihua Wang, Qi Cao, Yiping Wang and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 63 citations in OpenAlex.

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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 4 institutions in 2 countries.

Ye ZhaoCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Xi QiaoCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Thian Kui TanCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Hong ZhaoCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Yun ZhangCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Lixin LiuCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Jianlin ZhangCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Lihua WangDepartment of Nephrology, Second Hospital of Shanxi Medical University, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People's Republic of China.
Qi CaoCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Yiping WangCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Ya WangCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Yuan Min WangCentre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia.
Vincent W S LeeCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Stephen I AlexanderCentre for Kidney Research, Children's Hospital at Westmead, Sydney, NSW, Australia.
David C H HarrisCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Guoping ZhengCentre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
Westmead Institute for Medical Research · AUUniversity of Sydney · AUChildren's Hospital at Westmead · AUShanxi Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndothelial cells are known to contribute to kidney fibrosis via endothelial-mesenchymal transition (EndoMT). Matrix metalloproteinase 9 (MMP-9) is known to be profibrotic. However, whether MMP-9 contributes to kidney fibrosis via EndoMT is unknown.

methodsPrimary mouse renal peritubular endothelial cells (MRPECs) were isolated and treated by recombinant human transforming growth factor beta 1 (rhTGF-β1) with or without MMP-9 inhibitor or by recombinant human MMP-9 (rhMMP-9) alone. Kidney fibrosis was induced by unilateral ureteral obstruction (UUO) in MMP-9 knockout (KO) and wide-type (WT) control mice. The effects of MMP-9 on EndoMT of MRPECs and kidney fibrosis were examined.

resultsWe showed that MRPECs underwent EndoMT after rhTGF-β1 treatment or in UUO kidney as evidenced by decreased expression of endothelial markers, vascular endothelial cadherin (VE-cadherin) and CD31, and increased levels of mesenchymal markers, α-smooth muscle actin (α-SMA) and vimentin. The expression of fibrosis markers was also up-regulated significantly after rhTGF-β1 treatment in MRPECs. The EndoMT and fibrosis markers were significantly less in rhTGF-β1-treated MMP-9 KO MRPECs, whereas MMP-9 alone was sufficient to induce EndoMT in MRPECs. UUO kidney of MMP-9 KO mice showed significantly less interstitial fibrosis and EndoMT in MRPECs. Notch signaling shown by Notch intracellular domain (NICD) was increased, while Notch-1 was decreased in rhTGF-β1-treated MRPECs of MMP-9 WT but not MMP-9 KO mice. Inhibition of MMP-9 or Notch signaling prevented rhTGF-β1- or rhMMP-9-induced α-SMA and NICD upregulation in MRPECs. UUO kidney of MMP-9 KO mice had less staining of Notch signaling transcription factor Hey-1 in VE-cadherin-positive MRPECs than WT controls.

conclusionsOur results demonstrate that MMP-9-dependent Notch signaling plays an important role in kidney fibrosis through EndoMT of MRPECs.

Indexed as

AnimalsEndotheliumFibrosisHumansKidney DiseasesMaleMatrix Metalloproteinase 9MesodermMiceMice, Inbred BALB CMice, KnockoutReceptors, NotchSignal TransductionTransforming Growth Factor beta1Ureteral ObstructionMatrix Metalloproteinase 9Receptors, NotchTransforming Growth Factor beta1endothelial–mesenchymal transitionkidney fibrosisMatrix metalloproteinase 9Notchperitubular endothelial cells

Identifiers

PMID27566305
PMCPMC5427520
OpenAlexW2510280185

What OpenQuestion holds

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LicenceCC BY-NC
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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.