The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1
Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-β1 (TGF-β1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF...
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Frontiers Media S.A.
2021-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.732540/full |
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author | Yanhong Liu Yan Ding Yapeng Hou Tong Yu Hongguang Nie Yong Cui |
author_facet | Yanhong Liu Yan Ding Yapeng Hou Tong Yu Hongguang Nie Yong Cui |
author_sort | Yanhong Liu |
collection | DOAJ |
description | Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-β1 (TGF-β1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF, but the regulatory mechanisms are poorly understood. We co-cultured bone marrow-derived MSCs and mouse lung fibroblasts (MLg) in the presence of TGF-β1, and studied the protein/mRNA expression of fibrosis markers and related signaling pathways. The effects of miR-130a-3p and TGF-β receptor II (TGF-βRII) on the differentiation of MLg induced by TGF-β1 were studied using immunofluorescence assay, Western blot, and quantitative real-time PCR techniques, respectively. Our results showed that MSCs reversed the overexpression of fibrosis markers and TGF-β1/Smad signaling pathway proteins and mRNAs after TGF-β1 treatment and increased the level of miR-130a-3p. TGF-βRII was identified as a target of miR-130a-3p and was evaluated by dual-luciferase reporter assay. The miR-130a-3p/TGF-βRII axis could suppress the differentiation of lung fibroblasts via the TGF-β1/Smad signaling pathway, thereby reducing the process of PF. |
first_indexed | 2024-12-21T21:31:06Z |
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issn | 1663-9812 |
language | English |
last_indexed | 2024-12-21T21:31:06Z |
publishDate | 2021-07-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Pharmacology |
spelling | doaj.art-63a31c7dedac4e3ebc29a182aaaf279a2022-12-21T18:49:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.732540732540The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1Yanhong Liu0Yan Ding1Yapeng Hou2Tong Yu3Hongguang Nie4Yong Cui5Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, ChinaDepartments of Anesthesiology, The First Hospital of China Medical University, Shenyang, ChinaPulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-β1 (TGF-β1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF, but the regulatory mechanisms are poorly understood. We co-cultured bone marrow-derived MSCs and mouse lung fibroblasts (MLg) in the presence of TGF-β1, and studied the protein/mRNA expression of fibrosis markers and related signaling pathways. The effects of miR-130a-3p and TGF-β receptor II (TGF-βRII) on the differentiation of MLg induced by TGF-β1 were studied using immunofluorescence assay, Western blot, and quantitative real-time PCR techniques, respectively. Our results showed that MSCs reversed the overexpression of fibrosis markers and TGF-β1/Smad signaling pathway proteins and mRNAs after TGF-β1 treatment and increased the level of miR-130a-3p. TGF-βRII was identified as a target of miR-130a-3p and was evaluated by dual-luciferase reporter assay. The miR-130a-3p/TGF-βRII axis could suppress the differentiation of lung fibroblasts via the TGF-β1/Smad signaling pathway, thereby reducing the process of PF.https://www.frontiersin.org/articles/10.3389/fphar.2021.732540/fullpulmonary fibrosismesenchymal stem cellsmouse lung fibroblastmicroRNATGF-β1 |
spellingShingle | Yanhong Liu Yan Ding Yapeng Hou Tong Yu Hongguang Nie Yong Cui The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 Frontiers in Pharmacology pulmonary fibrosis mesenchymal stem cells mouse lung fibroblast microRNA TGF-β1 |
title | The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 |
title_full | The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 |
title_fullStr | The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 |
title_full_unstemmed | The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 |
title_short | The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1 |
title_sort | mir 130a 3p tgf βrii axis participates in inhibiting the differentiation of fibroblasts induced by tgf β1 |
topic | pulmonary fibrosis mesenchymal stem cells mouse lung fibroblast microRNA TGF-β1 |
url | https://www.frontiersin.org/articles/10.3389/fphar.2021.732540/full |
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