ArticleGenes & development2002
Disruption of the gene encoding the latent transforming growth factor-beta binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer.
Article in Genes & development, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled 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.
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
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 250 citations in OpenAlex.
- Association between theBioscience reports · 2017Pooled it
- A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.Human molecular genetics · 2012Pooled it
- SOX5 is a candidate gene for chronic obstructive pulmonary disease susceptibility and is necessary for lung development.American journal of respiratory and critical care medicine · 2011Trial
- LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice.Nature communications · 2026Article
- Constitutional epimutations in LTBP4, a component of the TGF-β signaling, and in BRCA1, as potential drivers of early-onset colorectal cancer.Clinical epigenetics · 2025Article
- APOE-NOTCH axis governs elastogenesis during human cardiac valve remodeling.Nature cardiovascular research · 2024Article
- Proteomic analysis of decellularized mice liver and kidney extracellular matrices.Journal of biological engineering · 2024Article
- Epigenetic identification of LTBP4 as a putative tumor suppressor in breast cancer.Epigenomics · 2024Article
- Potentiation of Sphingolipids and TGF-β in the human corneal stroma reveals intricate signaling pathway crosstalks.Experimental eye research · 2023Article
- Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation.Development (Cambridge, England) · 2023Article
- Humanization of the mdx Mouse Phenotype for Duchenne Muscular Dystrophy Modeling: A Metabolic Perspective.Journal of neuromuscular diseases · 2023Review
- Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers.Aging cell · 2022Article
- Article
- Structural studies of elastic fibre and microfibrillar proteins.Matrix biology plus · 2021Article
- LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure.Cell death & disease · 2021Article
- The Art of Engineering Biomimetic Cellular Microenvironments.ACS biomaterials science & engineering · 2021Article
- Mass Spectrometry-Based Proteomic Discovery of Prognostic Biomarkers in Adrenal Cortical Carcinoma.Cancers · 2021Article
- LTBP4 in Health and Disease.Genes · 2021Review
- Identification of a Novel Immune-Related CpG Methylation Signature to Predict Prognosis in Stage II/III Colorectal Cancer.Frontiers in genetics · 2021Article
- Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4.Frontiers in genetics · 2021Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-betas (TGF-betas) are multifunctional growth factors that are secreted as inactive (latent) precursors in large protein complexes. These complexes include the latency-associated propeptide (LAP) and a latent transforming growth factor-beta binding protein (LTBP). Four isoforms of LTBPs (LTBP-1-LTBP-4) have been cloned and are believed to be structural components of connective tissue microfibrils and local regulators of TGF-beta tissue deposition and signaling. By using a gene trap strategy that selects for integrations into genes induced transiently during early mouse development, we have disrupted the mouse homolog of the human LTBP-4 gene. Mice homozygous for the disrupted allele develop severe pulmonary emphysema, cardiomyopathy, and colorectal cancer. These highly tissue-specific abnormalities are associated with profound defects in the elastic fiber structure and with a reduced deposition of TGF-beta in the extracellular space. As a consequence, epithelial cells have reduced levels of phosphorylated Smad2 proteins, overexpress c-myc, and undergo uncontrolled proliferation. This phenotype supports the predicted dual role of LTBP-4 as a structural component of the extracellular matrix and as a local regulator of TGF-beta tissue deposition and signaling.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.