Atractylon Treatment Attenuates Pulmonary Fibrosis via Regulation of the mmu_circ_0000981/miR-211-5p/TGFBR2 Axis in an Ovalbumin-Induced Asthma Mouse Model.

Abstract

Asthma-induced pulmonary fibrosis (PF) is an important public health concern that has few treatment options given its poorly understood etiology; however, the epithelial to mesenchymal transition (EMT) of pulmonary epithelial cells has been implicated to play an important role in inducing PF. Although previous studies have found atractylon (Atr) to have anti-inflammatory effects, whether Atr has anti-PF abilities remains unknown. The purpose of the current study was to validate the protective efficiency of Atr in both an animal model of ovalbumin (OVA)-induced asthma and an EMT model induced by transforming growth factor-β1 (TGF-β1) using TC-1 cells. The results of this study revealed that Atr treatment suppressed OVA-induced PF via fibrosis-related protein expression. Atr treatment suppressed OVA-induced circRNA-0000981 and TGFBR2 expression but promoted miR-211-5p expression. In vivo studies revealed that Atr suppressed TGF-β1-induced EMT and fibrosis-related protein expression via suppressing circRNA-0000981 and TGFBR2 expression. The results also suggested that the downregulation of circRNA-0000981 expression suppressed TGFBR2 by sponging miR-211-5p, which was validated by a luciferase reporter assay. Collectively, the findings of the present study suggest that Atr treatment attenuates PF by regulating the mmu_circ_0000981/miR-211-5p/TGFBR2 axis in an OVA-induced asthma mouse model.

• Authors: Haizhu Zeng, Hongchang Gao, Meilan Zhang, Jinrui Wang, Yuxia Gu, Yumeng Wang, Huali Zhang, Panpan Liu, Xia Zhang, Lei Zhao
• Journal: Inflammation (Inflammation) Vol. 44 Issue 5 Pg. 1856-1864 (Oct 2021) ISSN: 1573-2576 [Electronic] United States
• PMID: 33855682 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• MicroRNAs
• Mirn211 microRNA, mouse
• RNA, Circular
• Sesquiterpenes
• atractylon
• Ovalbumin
• Receptor, Transforming Growth Factor-beta Type II
• Tgfbr2 protein, mouse

Topics

• Animals
• Asthma (chemically induced, drug therapy, metabolism)
• Cell Line
• Male
• Mice
• Mice, Inbred BALB C
• MicroRNAs (biosynthesis)
• Ovalbumin (toxicity)
• Pulmonary Fibrosis (chemically induced, metabolism, prevention & control)
• RNA, Circular (antagonists & inhibitors, biosynthesis)
• Receptor, Transforming Growth Factor-beta Type II (antagonists & inhibitors, biosynthesis)
• Sesquiterpenes (pharmacology, therapeutic use)
• Treatment Outcome