The effects of the miR-21/SMAD7/TGF-β pathway on Th17 cell differentiation in COPD
| Autor: | Zhengpeng Zeng, Shenghua Sun, Lihua Xie, Mubin Zhong, Shengyang He, Xiang Mei, Lili Chen, Liqiu Li, Junjuan Lu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Lymphoproliferative disorders CD4-Positive T-Lymphocytes Cell signaling Lung Neoplasms Science Cellular differentiation Immunology SMAD Lymphocyte Activation Article Cigarette Smoking Smad7 Protein Pathogenesis 03 medical and health sciences Mice Pulmonary Disease Chronic Obstructive 0302 clinical medicine RAR-related orphan receptor gamma Transforming Growth Factor beta Smoke medicine Animals Humans Lung cancer Lung Immunological disorders COPD Multidisciplinary business.industry Cell Differentiation Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Cancer research Medicine Th17 Cells business Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Chronic obstructive pulmonary disease (COPD) is a complex disease with multiple etiologies, while smoking is the most established one. The present study investigated the modulation of T-helper 17 (Th17) cell differentiation by the miR-21/Smad7/TGF-β pathway, and their roles in COPD. Lung tissues were obtained from lung cancer patients with or without COPD who underwent lobotomy and the levels of miR-21, TGF-β/Smad signaling molecules, RORγT, and other Th17-related cytokines were detected. Mouse COPD models were built by exposing both wild-type (WT) and miR-21−/− mice to cigarette smoke (CS) and cigarette smoke extract (CSE) intraperitoneal injection. Isolated primary CD4+ T cells were treated with either CS extract, miR-21 mimics or inhibitors, followed by measuring Th17 cells markers and the expression of TGF-β/Smad signaling molecules and RORγT. Increased levels of miR-21, Smad7, phosphorylated (p)-Smad2, p-Smad3, TGF-β, and Th17-related cytokines was detected in the lungs of COPD patients. Lung function in modeled WT mice, but not miR-21−/− ones, deteriorated and the number of inflammatory cells in the lung tissues increased compared to the control WT-mice. Moreover, primary CD4+ lymphocytes tend to differentiate into Th17 cells after the treatment with CSE or miR-21 mimics, and the expression of RORγT and the TGF-β/Smad signaling were all increased, however miR-21 inhibitors worked reversely. Our findings demonstrated that Th17 cells increased under COPD pathogenesis and was partially modulated by the miR-21/Smad7/TGF-β pathway. |
| Databáze: | OpenAIRE |
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