ArticleThe Journal of biological chemistry2018
LEM domain-containing protein 3 antagonizes TGFβ-SMAD2/3 signaling in a stiffness-dependent manner in both the nucleus and cytosol.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 28 citations in OpenAlex.
- Integration of nuclear mechanosensing with integrin-extracellular matrix adhesions.Nucleus (Austin, Tex.) · 2026Review
- Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT.Annals of biomedical engineering · 2026Review
- TGF‑β1 in obstructive sleep apnea: linking intermittent hypoxia, upper‑airway remodeling, and systemic comorbidities.Sleep & breathing = Schlaf & Atmung · 2026Review
- Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential.Biomolecules · 2026Review
- MicroRNA-mediated mechanotransduction and chondrocyte differentiation in mesenchymal stem cells.Animal cells and systems · 2026Review
- From Fibrosis to Malignancy: Mechanistic Intersections Driving Lung Cancer Progression.Cancers · 2025Review
- Keratinocyte self-renewal and differentiation is dictated by extrinsic signals from dermal extracellular matrices.Open biology · 2025Article
- Circular RNAs in Liver Diseases.Advances in experimental medicine and biology · 2025Review
- Regulatory Functions and Mechanisms of Circular RNAs in Hepatic Stellate Cell Activation and Liver Fibrosis.Cells · 2023Review
- From mesenchymal niches to engineeredMaterials today. Bio · 2022Article
- MicroRNAs in Mechanical Homeostasis.Cold Spring Harbor perspectives in medicine · 2022Review
- The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation.The Journal of biological chemistry · 2022Review
- Review
- The Diverse Cellular Functions of Inner Nuclear Membrane Proteins.Cold Spring Harbor perspectives in biology · 2021Review
- Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links.Biomolecules · 2021Review
- Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis.Frontiers in pharmacology · 2021Review
- Spatial-omics: Novel approaches to probe cell heterogeneity and extracellular matrix biology.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- A Report of a Novel Pathogenic Variant in a Family with Buschke-Ollendorf Syndrome.Journal of pediatric genetics · 2020Article
- Article
- Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis.Molecular biology of the cell · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Transforming growth factor-β (TGFβ) signaling through SMAD2/3 is an important driver of pathological fibrosis in multiple organ systems. TGFβ signaling and extracellular matrix (ECM) stiffness form an unvirtuous pathological circuit in which matrix stiffness drives activation of latent TGFβ, and TGFβ signaling then drives cellular stress and ECM synthesis. Moreover, ECM stiffness also appears to sensitize cells to exogenously activated TGFβ through unknown mechanisms. Here, using human fibroblasts, we explored the effect of ECM stiffness on a putative inner nuclear membrane protein, LEM domain-containing protein 3 (LEMD3), which is physically connected to the cell's actin cytoskeleton and inhibits TGFβ signaling. We showed that LEMD3-SMAD2/3 interactions are inversely correlated with ECM stiffness and TGFβ-driven luciferase activity and that LEMD3 expression is correlated with the mechanical response of the TGFβ-driven luciferase reporter. We found that actin polymerization but not cellular stress or LEMD3-nuclear-cytoplasmic couplings were necessary for LEMD3-SMAD2/3 interactions. Intriguingly, LEMD3 and SMAD2/3 frequently interacted in the cytosol, and we discovered LEMD3 was proteolytically cleaved into protein fragments. We confirmed that a consensus C-terminal LEMD3 fragment binds SMAD2/3 in a stiffness-dependent manner throughout the cell and is sufficient for antagonizing SMAD2/3 signaling. Using human lung biopsies, we observed that these nuclear and cytosolic interactions are also present in tissue and found that fibrotic tissues exhibit locally diminished and cytoplasmically shifted LEMD3-SMAD2/3 interactions, as noted
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.