| First Author | He S | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 6338 |
| PubMed ID | 33739023 | Mgi Jnum | J:305024 |
| Mgi Id | MGI:6695569 | Doi | 10.1038/s41598-021-85637-0 |
| Citation | He S, et al. (2021) The effects of the miR-21/SMAD7/TGF-beta pathway on Th17 cell differentiation in COPD. Sci Rep 11(1):6338 |
| abstractText | 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-beta 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-beta/Smad signaling molecules, RORgammaT, 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-beta/Smad signaling molecules and RORgammaT. Increased levels of miR-21, Smad7, phosphorylated (p)-Smad2, p-Smad3, TGF-beta, 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 RORgammaT and the TGF-beta/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-beta pathway. |
