O8G Site-specifically modified trf-1-aspgtc: A novel therapeutic target and biomarker for pulmonary hypertension

Zhang，Junting1,2,3,4; Li，Yiying1,2,3; Chen，Yuan1,5; Zhang，Jianchao1,2; Jia，Zihui1,2,3; He，Muhua1,2,3; Liao，Xueyi1,2; He，Siyu1,2,3; Bian，Jin Song1,2,3; Nie，Xiao Wei1,2

2024-06-21

10.1161/CIRCRESAHA.124.324421

Circulation Research   影响因子和分区

0009-7330

1524-4571

BACKGROUND: Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. We aimed to gain insight into the mechanistic contribution of oxidative stress-induced 8-oxoguanine in pulmonary vascular remodeling. METHODS: Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine -modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH. RESULTS: This modification occurs at the position 5 of the tRF-1-AspGTC (5o8G tRF). Inhibition of the 5o8G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o8G tRF retargeted mRNA of WNT5A (Wingless-type MMTV integration site family, member 5A) and CASP3 (Caspase3) and inhibited their expression. Ultimately, BMPR2 (Bone morphogenetic protein receptor 2) -reactive oxygen species/5o8G tRF/WNT5A signaling pathway exacerbated the progression of PH. CONCLUSIONS: Our study highlights the role of site-specific 8-oxoguanine-modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o8G tRF as a potential innovative marker for diagnosing this disease.

blood pressure cell proliferation hypertension reactive oxygen species vascular remodeling

SCI

英语

其他

CLINICAL MEDICINE

2-s2.0-85196525367

Scopus

1.Shenzhen Institute of Respiratory Disease,Shenzhen Key Laboratory of Respiratory Disease,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,China
2.The First Affiliated Hospital,Southern University of Science and Technology),China
3.Post-Doctoral Scientific Research Station of Basic Medicine,Jinan University,Guangzhou,China
4.Department of Pharmacology,Joint Laboratory of Guangdong-Hong Kong,Universities for Vascular Homeostasis and Diseases,School of Medicine,Southern University of Science and Technology,Shenzhen,China
5.Lung Transplant Group,Wuxi People's Hospital Affiliated to Nanjing Medical University,China

Zhang，Junting,Li，Yiying,Chen，Yuan,et al. O8G Site-specifically modified trf-1-aspgtc: A novel therapeutic target and biomarker for pulmonary hypertension[J]. Circulation Research,2024,135(1):76-92.

Zhang，Junting.,Li，Yiying.,Chen，Yuan.,Zhang，Jianchao.,Jia，Zihui.,...&Nie，Xiao Wei.(2024).O8G Site-specifically modified trf-1-aspgtc: A novel therapeutic target and biomarker for pulmonary hypertension.Circulation Research,135(1),76-92.

Zhang，Junting,et al."O8G Site-specifically modified trf-1-aspgtc: A novel therapeutic target and biomarker for pulmonary hypertension".Circulation Research 135.1(2024):76-92.