ArticleRespiratory research2023
TGFβ1-RCN3-TGFBR1 loop facilitates pulmonary fibrosis by orchestrating fibroblast activation.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Ubiquitination-Related Diagnostic Biomarkers for Diabetic Nephropathy: Insights From Multiomic Analysis, Drug Docking, and Experimental Validation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Effect of reticulocalbin 3 on monocyte-to-macrophage differentiation in sepsis through modulating autophagy.Chinese medical journal · 2026Article
- TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Cells · 2026Review
- Secreted RCN3 acts as an early epithelial-fibroblast mediator via TGFβR1-Smad signaling in post-ALI pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- A nanosystem targeting tissue inhibitor of metalloproteinase-1 for continuous spatiotemporal idiopathic pulmonary fibrosis therapy.Nature communications · 2026Article
- Integrating single-cell and bulk RNA-Seq to unravel the molecular mechanisms of airway stenosis.Functional & integrative genomics · 2025Article
- Unveiling the Therapeutic Potential: A Peptide Drug Conjugate's Influence on Transcription and Translation in Ocular Fibrosis Modulation.ACS omega · 2025Article
- RCN3 functions as a tumor promoter in colorectal cancer by modulating the GRP78-PI3K-AKT signaling pathway.Oncogene · 2025Article
- Proteomic Biomarkers of Survival in Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Disease.American journal of respiratory and critical care medicine · 2025Article
- RNA Sequencing Reveals Inflammatory and Metabolic Changes in the Lung and Brain After Carbon Black and Naphthalene Whole Body Inhalation Exposure in a Rodent Model of Military Burn Pit Exposures.International journal of molecular sciences · 2025Article
- Observational
- TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) bears high mortality due to unclear pathogenesis and limited therapeutic options. Therefore, identifying novel regulators is required to develop alternative therapeutic strategies.
methodsThe lung fibroblasts from IPF patients and Reticulocalbin 3 (RCN3) fibroblast-selective knockdown mouse model were used to determine the importance of Rcn3 in IPF; the epigenetic analysis and protein interaction assays, including BioID, were used for mechanistic studies.
resultsReticulocalbin 3 (RCN3) upregulation is associated with the fibrotic activation of lung fibroblasts from IPF patients and Rcn3 overexpression blunts the antifibrotic effects of pirfenidone and nintedanib. Moreover, repressing Rcn3 expression in mouse fibroblasts ameliorates bleomycin-induced lung fibrosis and pulmonary dysfunction in vivo. Mechanistically, RCN3 promotes fibroblast activation by maintaining persistent activation of TGFβ1 signalling via the TGFβ1-RCN3-TGFBR1 positive feedback loop, in which RCN3 upregulated by TGFβ1 exposure detains EZH2 (an epigenetic methyltransferase) in the cytoplasm through RCN3-EZH2 interaction, leading to the release of the EZH2-H3K27me3 epigenetic repression of TGFBR1 and the persistent expression of TGFBR1.
conclusionsThese findings introduce a novel regulating mechanism of TGFβ1 signalling in fibroblasts and uncover a critical role of the RCN3-mediated loop in lung fibrosis. RCN3 upregulation may cause resistance to IPF treatment and targeting RCN3 could be a novel approach to ameliorate pulmonary fibrosis.
Indexed as
Identifiers
What Socratic holds
Registered trials
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.