Evidence map›Paper›PMID 42345538›Full record

ArticleAmerican journal of respiratory cell and molecular biology2026

NF-κB-Dependent Transcriptional Regulation of Piezo1 Mediates Bacterial Clearance on Infected Lung Stiffness.

Erica M Orsini, Adam M Boulton, Susamma Abraham, Alyson Brown, Haley Ricci, Akash Ahuja, Bishnu Pant, Caitlin M Snyder, Amanda Reinhardt, Amy H Attaway and 5 more

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Article in American journal of respiratory cell and molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Erica M OrsiniIntegrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.ORCID 0000-0003-2805-4783
Adam M BoultonInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Susamma AbrahamInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Alyson BrownCleveland Clinic Lerner College of Medicine, Cleveland, OH.
Haley RicciInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Akash AhujaInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Bishnu PantInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Caitlin M SnyderInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Amanda ReinhardtInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Amy H AttawayIntegrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.
Ryan MusichInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Lisa M GroveInflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH.
Mitchell A OlmanIntegrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.
Vidula VachharajaniIntegrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.
Rachel G ScheragaIntegrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.ORCID 0000-0001-5113-543X

Funding

TRPV4 Regulates Mechanosensitive Macrophage Functions in Lung InjuryR01HL155064 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI SCHERAGA, RACHEL GREENBERG · 2021 to 2025
$2.1M
NHLBI NIH HHS R01 HL155064
6 · The paper itself

Abstract

rationaleRespiratory pathogens, such as Pseudomonas aeruginosa damage the alveolar-capillary barrier leading to lung injury and stiffness. Lung stiffness is a key macrophage signal for bacterial clearance, but it remains unknown how stiffness-sensing mechanosensitive ion channels in macrophages are regulated during pneumonia. Macrophage Piezo1 is critical to bacterial clearance in experimental pneumonia in vivo; however, identification of putative matrix-derived signals and the mechanism of their effects remain to be determined.

objectivesWe investigated the role of P. aeruginosa virulence factors on Piezo1 activity in macrophages on infected lung matrix stiffness.

methodsUsing bone-marrow derived macrophages, we measured Piezo1 abundance and function and bacterial clearance in response to P. aeruginosa virulence factors on pathophysiologic range lung stiffnesses and standard tissue culture conditions. MEASUREMENTS AND MAIN

resultsTo our knowledge, our work is the first to show that during pneumonia, transcription of the mechanosensitive ion channel Piezo1 is increased in macrophages by the NF-κB transcription factor, p65, through its signaling adaptor protein, MyD88, leading to increased Piezo1 Ca2 + channel activity. Piezo1 mRNA abundance is increased in association with open chromatin at the Piezo1 promoter in macrophages. The enhanced level of Piezo1 increases the abundance of transcription factor EB (Tfeb) resulting in lysosome biogenesis and stiffness-dependent phagolysosome maturation, a critical step for macrophage bacterial clearance.

conclusionsOur data support the mechanism whereby transcription of macrophage Piezo1 is enhanced by p65 to augment bacterial clearance on an injured, stiffened lung matrix during pneumonia. Therefore, Piezo1 is a future therapeutic target against pneumonia-induced lung injury.

Identifiers

PMID42345538
PMCPMC13317738

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