Evidence map›Paper›PMID 38824643›Full record

ArticleCell reports2024

FAK regulates tension transmission to the nucleus and endothelial transcriptome independent of kinase activity.

Md Zahid Akhter, Pascal Yazbeck, Mohammad Tauseef, Mumtaz Anwar, Faruk Hossen, Sayanti Datta, Vigneshwaran Vellingiri, Jagdish Chandra Joshi, Peter T Toth, Nityanand Srivastava and 6 more

Abstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
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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.

Md Zahid AkhterDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Pascal YazbeckDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Mohammad TauseefDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Mumtaz AnwarDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Faruk HossenDepartment of Biomedical Engineering, Chicago, IL, USA.
Sayanti DattaDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Vigneshwaran VellingiriDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Jagdish Chandra JoshiDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Peter T TothDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA; Research Resources Center, University of Illinois, Chicago, IL, USA.
Nityanand SrivastavaDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Stephen LenziniDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA.
Guangjin ZhouDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
James LeeDepartment of Biomedical Engineering, Chicago, IL, USA.
Mukesh K JainDivision of Biology and Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Jae-Won ShinDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA; Department of Biomedical Engineering, Chicago, IL, USA.
Dolly MehtaDepartment of Pharmacology & Regenerative Medicine and Center for Lung and Vascular Biology, Chicago, IL, USA. Electronic address: dmehta@uic.edu.

Funding

The Lung Endothelium as an Instructive Niche for the Innate Immune System during Vascular InjuryP01HL160469 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Jalees Rehman · 2022 to 2026
$14.0M
Synthetic Biology and Optogenetics CoreP01HL151327 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI REHMAN, JALEES · 2021 to 2025
$11.8M
Focal Adhesion Kinase Regulation of Lung Vascular Permeability and EdemagenesisR01HL084153 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MEHTA, DOLLY · 2007 to 2022
$5.4M
Roles of Tau Oligomers in Alzheimer's VasculopathyR01AG044404 · NIA · UNIVERSITY OF MISSOURI-COLUMBIA · PI LEE, JAMES C · 2014 to 2024
$3.5M
Targeting mechanisms activating ion-channel for preventing acute lung injuryR01HL165263 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 2023 to 2026
$2.4M
Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosisR01HL141255 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHIN, JAE-WON · 2019 to 2023
$2.0M
Engineering microscale hydrogel deposition to direct single stem cell differentiationR01GM141147 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHIN, JAE-WON · 2021 to 2024
$1.9M
Therapeutic nanoscale matrimeresR01EB034507 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHIN, JAE-WON · 2023 to 2025
$1.3M
NHLBI NIH HHS P01 HL151327NHLBI NIH HHS P01 HL160469NHLBI NIH HHS R01 HL084153NHLBI NIH HHS R01 HL141255NHLBI NIH HHS R01 HL165263NIA NIH HHS R01 AG044404NIBIB NIH HHS R01 EB034507NIGMS NIH HHS R01 GM141147
6 · The paper itself

Abstract

The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with the matrix controls nuclear tension, preventing aberrant gene synthesis and the transition from restrictive to leaky endothelium, a hallmark of acute lung injury (ALI). However, the mechanisms controlling tension transmission to the nucleus and EC-restrictive fate remain elusive. Here, we demonstrate that, in a kinase-independent manner, focal adhesion kinase (FAK) safeguards tension transmission to the nucleus to maintain EC-restrictive fate. In FAK-depleted ECs, robust activation of the RhoA-Rho-kinase pathway increased EC tension and phosphorylation of the nuclear envelope protein, emerin, activating DNMT3a. Activated DNMT3a methylates the KLF2 promoter, impairing the synthesis of KLF2 and its target S1PR1 to induce the leaky EC transcriptome. Repleting FAK (wild type or kinase dead) or inhibiting RhoA-emerin-DNMT3a activities in damaged lung ECs restored KLF2 transcription of the restrictive EC transcriptome. Thus, FAK sensing and control of tension transmission to the nucleus govern restrictive endothelium to maintain lung homeostasis.

Indexed as

Cell NucleusEndothelial CellsKruppel-Like Transcription FactorsrhoA GTP-Binding ProteinTranscriptomeAnimalsDNA Methyltransferase 3AFemaleFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesHumansHuman Umbilical Vein Endothelial CellsMaleMembrane ProteinsMiceNuclear ProteinsDNA Methyltransferase 3ADNMT3A protein, humanFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesKLF2 protein, humanKruppel-Like Transcription FactorsMembrane ProteinsNuclear ProteinsPTK2 protein, humanPtk2 protein, mouserhoA GTP-Binding Proteinrho-Associated KinasesCP: Cell biologyDNA methylationDNMT3aemerinendothelial cellFAKintracellular tensionKLF2S1PR1stiffness

Identifiers

PMID38824643
PMCPMC11262709

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.