ArticleMolecular and cellular endocrinology2018
Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.
Article in Molecular and cellular endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Sex differences in adult asthma and COPD therapy: a systematic review.Respiratory research · 2022Pooled it
- AhR activation inhibits DRP1-induced mitochondrial fission in airway smooth muscle during asthma.American journal of respiratory cell and molecular biology · 2026Article
- Overactive PDGFRα and PDGFRβ promote distinct phenotypes of skeletal muscle fibrosis and stiffness, with PDGFRβ also driving muscle growth.American journal of physiology. Cell physiology · 2026Article
- The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions.Clinical reviews in allergy & immunology · 2026Review
- Overactive PDGFRα and PDGFRβ promote distinct yet overlapping phenotypes of skeletal muscle fibrosis and stiffness, with PDGFRβ also driving drastic muscle growth.bioRxiv : the preprint server for biology · 2026Article
- Pharmacotherapeutic considerations of selective estrogen receptor modulators for vascular protection.Frontiers in pharmacology · 2026Review
- Increased platelet counts are associated with female sex and asthma severity.The journal of allergy and clinical immunology. Global · 2025Article
- Asthma and inflammation transcriptionally up-regulate the aryl hydrocarbon receptor in airway smooth muscle via p38/JNK-AP1 signalling.British journal of pharmacology · 2025Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- Kiss1 receptor knockout exacerbates airway hyperresponsiveness and remodeling in a mouse model of allergic asthma.Respiratory research · 2024Article
- Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell Migration.American journal of respiratory cell and molecular biology · 2024Article
- Downregulation of protein phosphatase 2Aα in asthmatic airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Transcriptomics analysis of allergen-induced inflammatory gene expression in the Four-Core Genotype mouse model.Physiological genomics · 2024Article
- Estrogen receptors differentially modifies lamellipodial and focal adhesion dynamics in airway smooth muscle cell migration.Molecular and cellular endocrinology · 2024Article
- Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma.International journal of molecular sciences · 2023Review
- Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma.The Journal of pathology · 2023Article
- Steady-state estradiol triggers a unique innate immune response to allergen resulting in increased airway resistance.Biology of sex differences · 2023Article
- Molecular determinants of airway smooth muscle cells in health and disease.Annals of translational medicine · 2022Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways, and may point to a novel perception for blunting airway remodeling.
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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.