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Int J Biol Sci 2023; 19(10):3042-3056. doi:10.7150/ijbs.80140 This issue Cite

Research Paper

FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis

Hailong Li1*, Jinhe Li1,2*, Yayue Hu1,2*, Ruotong Zhang1,2, Xiaoting Gu1, Yiying Wei1,2, Shanshan Zhang1,2, Xuefen Chen3, Luqing Wei4, Xiaohe Li1,2, Songtao Gu5, Jin Jin6, Hui Huang7✉, Honggang Zhou1,2✉, Cheng Yang1,2✉

1. The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University.
2. High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
3. Department of Respiratory Medicine, Characteristic Medical Center of the Chinese People's Armed Police Force, Tianjin, China.
4. Department of Respiratory and Critical Care Medicine, Tianjin Beichen Hospital, No. 7 Beiyi Road, Beichen District, Tianjin 300400, China.
5. Department of Respiratory & Critical Care Medicine,Tianjin Chest Hospital,No.261,Taierzhuang South Road, Jinnan District,Tianjin 300222,China.
6. Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Beijing 100730, People's Republic of China.
7. Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
*These authors contributed equally: Hai-long Li, Jinhe Li and Yayue Hu

✉ Corresponding authors: Hui Huang (pumchhhcom); Honggang Zhou (honggang.zhouedu.cn); Cheng Yang (yangchengedu.cn).

Citation:
Li H, Li J, Hu Y, Zhang R, Gu X, Wei Y, Zhang S, Chen X, Wei L, Li X, Gu S, Jin J, Huang H, Zhou H, Yang C. FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. Int J Biol Sci 2023; 19(10):3042-3056. doi:10.7150/ijbs.80140. https://www.ijbs.com/v19p3042.htm
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Abstract

Graphic abstract

Forkhead box protein O3 (FOXO3) has good inhibition ability toward fibroblast activation and extracellular matrix, especially for the treatment of idiopathic pulmonary fibrosis. How FOXO3 regulates pulmonary fibrosis remains unclear. In this study, we reported that FOXO3 had binding sequences with F-spondin 1 (SPON1) promoter, which can activate its transcription and selectively promote the expression of SPON1 circRNA (circSPON1) but not mRNA expression. We further demonstrated that circSPON1 was involved in the extracellular matrix deposition of HFL1. In the cytoplasm, circSPON1 directly interacted with TGF-β1-induced Smad3 and inhibited the activation of fibroblasts by inhibiting nuclear translocation. Moreover, circSPON1 bound to miR-942-5p and miR-520f-3p that interfered with Smad7 mRNA and promoted Smad7 expression. This study revealed the mechanism of FOXO3-regulated circSPON1 in the development of pulmonary fibrosis. Potential therapeutic targets and new insights into the diagnosis and treatment of idiopathic pulmonary fibrosis based on circRNA were also provided.

Keywords: Idiopathic pulmonary fibrosis, FOXO3, circSPON1, Smad3, Smad7

Citation styles

APA
Li, H., Li, J., Hu, Y., Zhang, R., Gu, X., Wei, Y., Zhang, S., Chen, X., Wei, L., Li, X., Gu, S., Jin, J., Huang, H., Zhou, H., Yang, C. (2023). FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. International Journal of Biological Sciences, 19(10), 3042-3056. https://doi.org/10.7150/ijbs.80140.

ACS
Li, H.; Li, J.; Hu, Y.; Zhang, R.; Gu, X.; Wei, Y.; Zhang, S.; Chen, X.; Wei, L.; Li, X.; Gu, S.; Jin, J.; Huang, H.; Zhou, H.; Yang, C. FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. Int. J. Biol. Sci. 2023, 19 (10), 3042-3056. DOI: 10.7150/ijbs.80140.

NLM
Li H, Li J, Hu Y, Zhang R, Gu X, Wei Y, Zhang S, Chen X, Wei L, Li X, Gu S, Jin J, Huang H, Zhou H, Yang C. FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. Int J Biol Sci 2023; 19(10):3042-3056. doi:10.7150/ijbs.80140. https://www.ijbs.com/v19p3042.htm

CSE
Li H, Li J, Hu Y, Zhang R, Gu X, Wei Y, Zhang S, Chen X, Wei L, Li X, Gu S, Jin J, Huang H, Zhou H, Yang C. 2023. FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis. Int J Biol Sci. 19(10):3042-3056.

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