Evidence map›Paper›PMID 29044509›Full record

ArticleJournal of cellular physiology2018

Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells.

Steven J Kunnen, Tareq B Malas, Cornelis M Semeins, Astrid D Bakker, Dorien J M Peters

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

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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

5 authors.

Steven J KunnenDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0001-9549-1719
Tareq B MalasDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Cornelis M SemeinsDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Astrid D BakkerDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Dorien J M PetersDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Renal epithelial cells are exposed to mechanical forces due to flow-induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction, and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano-sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid-shear regulated genes and pathways in renal epithelial cells. Functional enrichment-analysis revealed TGF-β, MAPK, and Wnt signaling as core signaling pathways up-regulated by shear. Inhibitors of TGF-β and MAPK/ERK signaling modulate a wide range of mechanosensitive genes, identifying these pathways as master regulators of shear-induced gene expression. However, the main down-regulated pathway, that is, JAK/STAT, is independent of TGF-β and MAPK/ERK. Other up-regulated cytokine pathways include FGF, HB-EGF, PDGF, and CXC. Cellular responses to shear are modified at several levels, indicated by altered expression of genes involved in cell-matrix, cytoskeleton, and glycocalyx remodeling, as well as glycolysis and cholesterol metabolism. Cilia ablation abolished shear induced expression of a subset of genes, but genes involved in TGF-β, MAPK, and Wnt signaling were hardly affected, suggesting that other mechano-sensors play a prominent role in the shear stress response of renal epithelial cells. Modulations in signaling due to variations in fluid shear stress are relevant for renal physiology and pathology, as suggested by elevated gene expression at pathological levels of shear stress compared to physiological shear.

Indexed as

Gene Expression ProfilingStress, MechanicalAnimalsCells, CulturedDown-RegulationEpithelial CellsGene ExpressionKidneyMice, TransgenicSignal TransductionUp-Regulationciliumfluid flowglycocalyxmechanotransductionnext generation sequencing

Identifiers

PMID29044509
PMCPMC5765508

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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.