ArticlePhysiological reports2020
Hypoxia and transforming growth factor β1 regulation of long non-coding RNA transcriptomes in human pulmonary fibroblasts.
Article in Physiological reports, 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, 26 citations in OpenAlex.
- Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.Journal of applied genetics · 2026Review
- Engineered atopic dermatitis models for recreating hypoxic conditions in atopic dermatitis microenvironments.Bioactive materials · 2026Article
- Distinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts.Journal of molecular and cellular cardiology plus · 2024Article
- Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases.Frontiers in pharmacology · 2024Review
- SNHG15 aids SARS-CoV-2 entry via RABL2A.RNA biology · 2023Article
- Regulation of influenza A virus infection by Lnc-PINK1-2:5.Journal of cellular and molecular medicine · 2022Article
- Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.eLife · 2022Article
- Article
- HuR drives lung fibroblast differentiation but not metabolic reprogramming in response to TGF-β and hypoxia.Respiratory research · 2021Article
- Bidirectional epithelial-mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis.The Journal of biological chemistry · 2021Article
- Long Noncoding RNAInternational journal of molecular sciences · 2021Article
- TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review).International journal of molecular medicine · 2021Review
- Long non-coding RNAs: Promising new targets in pulmonary fibrosis.The journal of gene medicine · 2021Review
- Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- Long Non-Coding RNAGenes · 2021Review
- Hyperbaric Oxygen Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice.Frontiers in molecular biosciences · 2021Article
- Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2020Article
- Hypoxia and transforming growth factor β1 regulation of long non-coding RNA transcriptomes in human pulmonary fibroblasts.Physiological reports · 2020Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
One of the key characteristics of idiopathic pulmonary fibrosis (IPF) is accumulation of excess fibrous tissue in the lung, which leads to hypoxic conditions. Transforming growth factor (TGF) β is a major mediator that promotes the differentiation of fibroblasts to myofibroblasts. However, how hypoxia and TGFβ together contribute the pathogenesis of IPF is poorly understood. Long non-coding RNAs (lncRNAs) have regulatory effects on certain genes and are involved in many diseases. In this study, we determined the effects of hypoxia and/or TGFβ on mRNA and lncRNA transcriptomes in pulmonary fibroblasts. Hypoxia and TGFβ1 synergistically increased myofibroblast marker expression. RNA sequencing revealed that hypoxia and TGFβ1 treatment resulted in significant changes in 669 lncRNAs and 2,676 mRNAs compared to 150 lncRNAs and 858 mRNAs in TGFβ1 alone group and 222 lncRNAs and 785 mRNAs in hypoxia alone group. TGFβ1 induced the protein expression of HIF-1α, but not HIF-2α. On the other hand, hypoxia enhanced the TGFβ1-induced phosphorylation of Smad3, suggesting a cross-talk between these two signaling pathways. In all, 10 selected lncRNAs (five-up and five-down) in RNA sequencing data were validated using real-time PCR. Two lncRNAs were primarily located in cytoplasm, three in nuclei and five in both nuclei and cytoplasm. The silencing of HIF-1α and Smad3, but not Smad2 and HIF-2α rescued the downregulation of FENDRR by hypoxia and TGFβ1. In conclusion, hypoxia and TGFβ1 synergistically regulate mRNAs and lncRNAs involved in several cellular processes, which may contribute to the pathogenesis of IPF.
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