---
title: "PIEZO1–YAP/TEAD Signaling Associates with POSTN-Enriched Fibroblast Activation in IPF"
id: "pubmed-42727476"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42727476"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42727476/"
doi: "10.1016/j.bbrc.2026.154515"
published_at: "2026-10-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PIEZO1–YAP/TEAD Signaling Associates with POSTN-Enriched Fibroblast Activation in IPF
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42727476
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42727476/)
- **DOI:** [10.1016/j.bbrc.2026.154515](https://doi.org/10.1016%2Fj.bbrc.2026.154515)
- **Published At:** 2026-10-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Investigators performed integrated analysis of public bulk lung transcriptomic datasets and identified a reproducible **POSTN**-enriched extracellular matrix remodeling program in idiopathic pulmonary fibrosis (IPF) lungs. - Single-cell and donor-level pseudobulk analyses indicated a co-enrichment of a **PIEZO1/YAP** activity–related signature specifically in POSTN-positive fibrotic fibroblast and myofibroblast compartments. - In a bleomycin-induced pulmonary fibrosis model, the study team observed Postn upregulation, Piezo1 induction, and increased Yap nuclear localization in fibrotic lung regions. - Verteporfin, employed as a pharmacologic inhibitor of Yap/TEAD-associated transcription, reduced collagen deposition, hydroxyproline accumulation, profibrotic gene expression, and Yap target protein induction in vivo according to the authors. - In TGF-β1–stimulated lung fibroblasts, verteporfin suppressed fibroblast migration, Yap nuclear localization, and profibrotic marker expression at concentrations the authors reported as non-cytotoxic. - Knockdown experiments showed that reducing Piezo1 or Yap1 expression decreased TGF-β1–induced fibroblast activation; Piezo1 knockdown also lowered Yap nuclear localization and Yap/TEAD reporter activity. - The study team found that expression of an active YAP construct partially restored profibrotic gene expression after Piezo1 knockdown, supporting **YAP/TEAD** as a downstream effector of **PIEZO1** signaling in fibroblasts. - Authors concluded that a POSTN-enriched fibrotic fibroblast state is associated with enhanced **PIEZO1–YAP/TEAD** signaling and that functional experiments support a role for this axis in fibroblast activation and fibrotic lung remodeling. - The abstract does not report detailed methods for dataset selection, sample sizes, dosing regimens for verteporfin, or specific quantitative outcome measures beyond the summary statements above.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 1. # PIEZO1 promotes YAP/TEAD-dependent profibrotic signaling in POSTN-enriched lung fibroblast activation [Xiaohua Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+X&cauthor_id=42727476)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#full-view-affiliation-1 "Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China."), [Jinping Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+J&cauthor_id=42727476)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#full-view-affiliation-2 "Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China."), [Aming Sang](https://pubmed.ncbi.nlm.nih.gov/?term=Sang+A&cauthor_id=42727476)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#full-view-affiliation-3 "Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. Electronic address: sangaming@163.com.") Affiliations Expand ### Affiliations * 1 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. * 2 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China. * 3 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. Electronic address: sangaming@163.com. * PMID: **42727476** * DOI: [ 10.1016/j.bbrc.2026.154515 ](https://doi.org/10.1016/j.bbrc.2026.154515) Item in Clipboard # PIEZO1 promotes YAP/TEAD-dependent profibrotic signaling in POSTN-enriched lung fibroblast activation Xiaohua Wang et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42727476/) . 2026 Oct 22:836:154515. doi: 10.1016/j.bbrc.2026.154515. Epub 2026 Sep 1. ### Authors [Xiaohua Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+X&cauthor_id=42727476)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#short-view-affiliation-1 "Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China."), [Jinping Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+J&cauthor_id=42727476)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#short-view-affiliation-2 "Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China."), [Aming Sang](https://pubmed.ncbi.nlm.nih.gov/?term=Sang+A&cauthor_id=42727476)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42727476/#short-view-affiliation-3 "Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. Electronic address: sangaming@163.com.") ### Affiliations * 1 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. * 2 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China. * 3 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei Province, 430071, China. Electronic address: sangaming@163.com. * PMID: **42727476** * DOI: [ 10.1016/j.bbrc.2026.154515 ](https://doi.org/10.1016/j.bbrc.2026.154515) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Idiopathic pulmonary fibrosis (IPF) is driven by persistent fibroblast activation, excessive extracellular matrix (ECM) deposition, and progressive tissue stiffening, yet the mechanosensitive signaling programs that sustain fibrotic fibroblast states remain incompletely defined. Here, we investigated the association between a periostin (POSTN)-enriched fibrotic program and PIEZO1-dependent Yes-associated protein (YAP)/TEA domain transcription factor (TEAD) activation in IPF. Integrated analysis of public bulk lung transcriptomic datasets identified a reproducible POSTN-enriched ECM remodeling program in IPF lungs. Single-cell and donor-level pseudobulk analyses further showed that a PIEZO1/YAP activity-related signature was co-enriched in POSTN-positive fibrotic fibroblast and myofibroblast compartments. In bleomycin-induced pulmonary fibrosis, Postn upregulation, Piezo1 induction, and increased Yap nuclear localization were recapitulated in fibrotic lung regions. Verteporfin, used as a pharmacological inhibitor of Yap/TEAD-associated transcription, attenuated collagen deposition, hydroxyproline accumulation, profibrotic gene expression, and Yap target protein induction in vivo. In transforming growth factor-β1 (TGF-β1)-stimulated lung fibroblasts, verteporfin suppressed fibroblast migration, Yap nuclear localization, and profibrotic marker expression at non-cytotoxic concentrations. Knockdown of Piezo1 or Yap1 reduced TGF-β1-induced fibroblast activation, while Piezo1 knockdown decreased Yap nuclear localization and Yap/TEAD reporter activity. Active YAP partially restored profibrotic gene expression after Piezo1 knockdown, supporting Yap/TEAD as an important downstream effector of Piezo1. Collectively, these findings identify an association between a POSTN-enriched fibrotic fibroblast state and enhanced PIEZO1-YAP/TEAD signaling, while functional experiments support a role for PIEZO1-YAP/TEAD in fibroblast activation and fibrotic lung remodeling. **Keywords:** Fibroblast activation; Idiopathic pulmonary fibrosis; PIEZO1; POSTN; YAP/TEAD. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ In vitro evaluation of Verteporfin and exploration of TEAD palmitoylation inhibition in Piezo1-YAP/TAZ signaling and ECM remodeling. ](https://pubmed.ncbi.nlm.nih.gov/41407746/) Xiaojun Z, Chen Q, Liu S, Liu B.Xiaojun Z, et al.Sci Rep. 2025 Dec 17;15(1):44048. doi: 10.1038/s41598-025-28960-0.Sci Rep. 2025.PMID: 41407746Free PMC article. * [ Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts. ](https://pubmed.ncbi.nlm.nih.gov/32192225/) Huang LS, Sudhadevi T, Fu P, Punathil-Kannan PK, Ebenezer DL, Ramchandran R, Putherickal V, Cheresh P, Zhou G, Ha AW, Harijith A, Kamp DW, Natarajan V.Huang LS, et al.Int J Mol Sci. 2020 Mar 17;21(6):2064. doi: 10.3390/ijms21062064.Int J Mol Sci. 2020.PMID: 32192225Free PMC article. * [ TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation. ](https://pubmed.ncbi.nlm.nih.gov/32159970/) Aravamudhan A, Haak AJ, Choi KM, Meridew JA, Caporarello N, Jones DL, Tan Q, Ligresti G, Tschumperlin DJ.Aravamudhan A, et al.Am J Physiol Lung Cell Mol Physiol. 2020 May 1;318(5):L852-L863. doi: 10.1152/ajplung.00324.2019. Epub 2020 Mar 11.Am J Physiol Lung Cell Mol Physiol. 2020.PMID: 32159970Free PMC article. * [ S100A4 Orchestrates Fibroblast Fate to Drive Fibrotic Remodeling. ](https://pubmed.ncbi.nlm.nih.gov/42287596/) Li S, Cai B, Zhang X, Cai G, Zhou Y, Wagener BM, Ding Q.Li S, et al.FASEB J. 2026 Jun 30;40(12):e72043. doi: 10.1096/fj.202600886R.FASEB J. 2026.PMID: 42287596Free PMC article. * [ YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis. ](https://pubmed.ncbi.nlm.nih.gov/39329703/) Papavassiliou KA, Sofianidi AA, Spiliopoulos FG, Gogou VA, Gargalionis AN, Papavassiliou AG.Papavassiliou KA, et al.Cells. 2024 Sep 10;13(18):1519. doi: 10.3390/cells13181519.Cells. 2024.PMID: 39329703Free PMC article.Review. 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