Hypoxia and transforming growth factor β1 regulation of long non‐coding RNA transcriptomes in human pulmonary fibroblasts

Autor: Chaoqun Huang, Dao Xu, Samuel Pushparaj, Lakmini Kumari Senavirathna, Lin Liu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Physiology
Smad2 Protein
030204 cardiovascular system & hematology
Biology
Real-Time Polymerase Chain Reaction
lcsh:Physiology
Cell Line
Transforming Growth Factor beta1
Transcriptome
03 medical and health sciences
TGFβ
0302 clinical medicine
lncRNA
Downregulation and upregulation
Physiology (medical)
Basic Helix-Loop-Helix Transcription Factors
medicine
Humans
Gene silencing
Respiratory Physiology
RNA
Messenger
Smad3 Protein
Phosphorylation
Myofibroblasts
Lung
Original Research
Messenger RNA
lcsh:QP1-981
hypoxia
RNA
Fibroblasts
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
Idiopathic Pulmonary Fibrosis
Long non-coding RNA
3. Good health
Cell biology
Gene Expression Regulation
RNA
Long Noncoding
Cellular Physiology
medicine.symptom
transcriptome
030217 neurology & neurosurgery
Transforming growth factor
Zdroj: Physiological Reports, Vol 8, Iss 1, Pp n/a-n/a (2020)
Physiological Reports
Popis: 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.
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. Hypoxia and TGFβ1 synergistically regulate mRNAs and lncRNAs involved in several cellular processes, which may contribute to the pathogenesis of IPF.
Databáze: OpenAIRE
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