ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
Transforming growth factor-β stimulates Smad1/5 signaling in pulmonary artery smooth muscle cells and fibroblasts of the newborn mouse through ALK1.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis 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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Pulmonary hypertension secondary to congenital diaphragmatic hernia: factors and pathways involved in pulmonary vascular remodeling.Pediatric research · 2019Pooled it
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
- Effect of the TGF-β/BMP Signaling Pathway on the Proliferation of Yak Pulmonary Artery Smooth Muscle Cells under Hypoxic Conditions.Animals : an open access journal from MDPI · 2024Article
- Nitric oxide regulation of fetal and newborn lung development and function.Nitric oxide : biology and chemistry · 2024Review
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- Role of magnesium-doped calcium sulfate and β-tricalcium phosphate composite ceramics in macrophage polarization and osteo-induction.Odontology · 2022Article
- Lysyl oxidase regulation and protein aldehydes in the injured newborn lung.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Strontium Regulates the Proliferation and Differentiation of Isolated Primary Bovine ChondrocytesFrontiers in pharmacology · 2022Article
- Article
- Platelet-Rich Fibrin Increases BMP2 Expression in Oral Fibroblasts via Activation of TGF-β Signaling.International journal of molecular sciences · 2021Article
- The role of Smad signaling cascades in cardiac fibrosis.Cellular signalling · 2021Review
- MiR-145 in cancer therapy resistance and sensitivity: A comprehensive review.Cancer science · 2020Review
- Transforming growth factor-β in tissue fibrosis.The Journal of experimental medicine · 2020Review
- S-endoglin expression is induced in hyperoxia and contributes to altered pulmonary angiogenesis in bronchopulmonary dysplasia development.Scientific reports · 2020Article
- Overexpression of NNT-AS1 Activates TGF-BioMed research international · 2020Article
- BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFβ responses and altered cell mechanics.PLoS biology · 2019Article
- Downregulation of miR‑98 contributes to hypoxic pulmonary hypertension by targeting ALK1.Molecular medicine reports · 2019Article
- miR-1306 Mediates the Feedback Regulation of the TGF-β/SMAD Signaling Pathway in Granulosa Cells.Cells · 2019Article
- Transforming growth factor-β downregulates sGC subunit expression in pulmonary artery smooth muscle cells via MEK and ERK signaling.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Roles of Smads Family and Alternative Splicing Variants of Smad4 in Different Cancers.Journal of Cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The intracellular signaling mechanisms through which TGF-β regulates pulmonary development are incompletely understood. Canonical TGF-β signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here, we show that physiologically relevant TGF-β1 levels also stimulate Smad1/5 phosphorylation, which is typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines. This cross-talk mechanism likely has in vivo relevance because mixed Smad1/5/8·Smad2/3 complexes, which are indicative of TGF-β-stimulated Smad1/5 activation, were detected in the developing mouse lung using a proximity ligation assay. Although mixed Smad complexes have been shown not to transduce nuclear signaling, we determined that TGF-β stimulates nuclear localization of phosphorylated Smad1/5 and induces the expression of prototypical BMP-regulated genes in the mPASMC. Small-molecule kinase inhibitor studies suggested that TGF-β-regulated Smad1/5 phosphorylation in these cells is mediated by TGF-β-type I receptors, not BMP-type I receptors, but possibly the accessory activin-like kinase (ALK1) receptor. Although work by others suggested that ALK1 is expressed exclusively in endothelial cells in the vasculature, we detected ALK1 mRNA and protein expression in mPASMC in vitro and in mouse pup lungs. Moreover, using an antimurine ALK1 antibody and mPASMC, we determined that ALK1 regulates Smad1/5 phosphorylation by TGF-β. Together, these studies characterize an accessory TGF-β-stimulated BMP R-Smad signaling mechanism in interstitial cells of the developing lung. They also indicate the importance of considering alternate Smad pathways in studies directed at determining how TGF-β regulates newborn lung development.
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.