ArticleJCI insight2020
Stiff matrix instigates type I collagen biogenesis by mammalian cleavage factor I complex-mediated alternative polyadenylation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Idiopathic pulmonary fibrosis from a multiscale mechanobiology perspective: Mechanisms and future therapeutic prospects.iScience · 2026Review
- MUUMI: an R package for statistical and network-based meta-analysis for multi-omics data integration.BMC bioinformatics · 2026Article
- CPSF6-mediated alternative polyadenylation of RUNX1 to regulate silica-induced pulmonary fibrosis progression.Respiratory research · 2026Article
- PKM2 mediates the glycolytic response to matrix stiffness in lung fibroblasts.Frontiers in cell and developmental biology · 2026Article
- Dynamic multi-omics and mechanistic modeling approach uncovers novel mechanisms of kidney fibrosis progression.Molecular systems biology · 2025Article
- An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease.JAMA network open · 2024Article
- Substrate Stiffness Modulates TGF-β Activation and ECM-Associated Gene Expression in Fibroblasts.Bioengineering (Basel, Switzerland) · 2023Article
- Article
- Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.Journal of translational medicine · 2022Article
- Substrate stiffness engineered to replicate disease conditions influence senescence and fibrotic responses in primary lung fibroblasts.Frontiers in pharmacology · 2022Article
- Emerging roles of alternative cleavage and polyadenylation (APA) in human disease.Journal of cellular physiology · 2022Review
- Article
- Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.The Journal of experimental medicine · 2021Article
- Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- Effective tools for RNA-derived therapeutics: siRNA interference or miRNA mimicry.Theranostics · 2021Review
- Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis.Frontiers in pharmacology · 2021Review
- You Say You Want a Resolution (of Fibrosis).American journal of respiratory cell and molecular biology · 2020Review
- Proteoglycans in Mechanobiology of Tissues and Organs: Normal Functions and Mechanopathology.Proteoglycan researchArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Alternative polyadenylation (APA) is a widespread and important mechanism in regulation of gene expression. Dysregulation of the 3' UTR cleavage and polyadenylation represents a common characteristic among many disease states, including lung fibrosis. In this study, we investigated the role of mammalian cleavage factor I-mediated (CFIm-mediated) APA in regulating extracellular matrix production in response to mechanical stimuli from stiffened matrix simulating the fibrotic lungs. We found that stiff matrix downregulated expression of CFIm68, CFIm59 and CFIm25 subunits and promoted APA in favor of the proximal poly(A) site usage in the 3' UTRs of type I collagen (COL1A1) and fibronectin (FN1) in primary human lung fibroblasts. Knockdown and overexpression of each individual CFIm subunit demonstrated that CFIm68 and CFIm25 are indispensable attributes of stiff matrix-induced APA and overproduction of COL1A1, whereas CFIm did not appear to mediate stiffness-regulated FN1 APA. Furthermore, expression of the CFIm subunits was associated with matrix stiffness in vivo in a bleomycin-induced mouse model of pulmonary fibrosis. These data suggest that stiff matrix instigates type I collagen biogenesis by selectively targeting mRNA transcripts for 3' UTR shortening. The current study uncovered a potential mechanism for regulation of the CFIm complex by mechanical cues under fibrotic conditions.
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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 OpenQuestion graph.