Evidence map›Paper›PMID 30303712›Full record

ArticleAmerican journal of physiology. Renal physiology2019

A conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition.

Eoghainín Ó hAinmhire, Haojia Wu, Yoshiharu Muto, Erinn L Donnelly, Flavia G Machado, Lucy X Fan, Monica Chang-Panesso, Benjamin D Humphreys

Open access · hybridAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Inactivation ofeLife · 2023
    Article
  7. Article
  8. Article
  9. Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Sonic Hedgehog Signaling and Tooth Development.International journal of molecular sciences · 2020
    Review
  17. 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

8 authors at 1 institution in 1 country.

Eoghainín Ó hAinmhireDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Haojia WuDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Yoshiharu MutoDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Erinn L DonnellyDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Flavia G MachadoDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Lucy X FanDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Monica Chang-PanessoDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.
Benjamin D HumphreysDivision of Nephrology, Department of Medicine, Washington University in Saint Louis School of Medicine , St. Louis, Missouri.ORCID 0000-0002-6420-8703
Washington University in St. Louis · US

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Coordinating Unit for DiaCompU24DK115255 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2017 to 2020
$11.6M
RENAL DISEASET32DK007126 · NIDDK · WASHINGTON UNIVERSITY · PI HUMPHREYS, BENJAMIN D. · 1986 to 2022
$5.2M
Understanding Myofibroblast Progenitor Fate and Function in Renal FibrosisR01DK103740 · NIDDK · WASHINGTON UNIVERSITY · PI BENJAMIN D. HUMPHREYS · 2015 to 2026
$3.9M
Adult Progenitors in Kidney TubulointerstitiumUH3DK107374 · NIDDK · WASHINGTON UNIVERSITY · PI HUMPHREYS, BENJAMIN D. · 2017 to 2019
$948k
Adult Progenitors in Kidney TubulointerstitiumUH2DK107374 · NIDDK · WASHINGTON UNIVERSITY · PI HUMPHREYS, BENJAMIN D. · 2015 to 2016
$626k
NIDDK NIH HHS R01 DK103740NIDDK NIH HHS T32 DK007126NIDDK NIH HHS U24 DK076169NIDDK NIH HHS U24 DK115255NIDDK NIH HHS UH2 DK107374NIDDK NIH HHS UH3 DK107374
6 · The paper itself

Abstract

Glioma-associated oncogene homolog-1 (Gli1)-positive resident mesenchymal stem cell-like cells are the predominant source of kidney myofibroblasts in fibrosis, but investigating Gli1-positive myofibroblast progenitor activation is hampered by the difficulty of isolating and propagating primary cultures of these cells. Using a genetic strategy with positive and negative selection, we isolated Kidney-Gli1 (KGli1) cells that maintain expression of appropriate mesenchymal stem cell-like cell markers, respond to hedgehog pathway activation, and display robust myofibroblast differentiation upon treatment with transforming growth factor-β (TGF-β). Coculture of KGli1 cells with endothelium stabilizes capillary formation. Single-cell RNA sequencing (scRNA-seq) analysis during differentiation identified autocrine ligand-receptor pair upregulation and a strong focal adhesion pathway signal. This led us to test the serum response factor inhibitor CCG-203971 that potently inhibited TGF-β-induced pericyte-to-myofibroblast transition. scRNA-seq also identified the unexpected upregulation of nerve growth factor (NGF), which we confirmed in two mouse kidney fibrosis models. The Ngf receptor Ntrk1 is expressed in tubular epithelium in vivo, suggesting a novel interstitial-to-tubule paracrine signaling axis. Thus, KGli1 cells accurately model myofibroblast activation in vitro, and the development of this cell line provides a new tool to study resident mesenchymal stem cell-like progenitors in health and disease.

Indexed as

Cell DifferentiationCell LineageAnimalsAntigens, Polyomavirus TransformingCell Line, TransformedCell SeparationCoculture TechniquesEpithelial-Mesenchymal TransitionFibrosisGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsKidneyMesenchymal Stem CellsMice, TransgenicMyofibroblastsAntigens, Polyomavirus TransformingGli1 protein, mouseZinc Finger Protein GLI1chronic kidney diseasefibrosismyofibroblastpericytesingle-cell RNA sequencingtranscriptomicstransforming growth factor-β

Identifiers

PMID30303712
PMCPMC6383201
OpenAlexW2896677975

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.