دورية أكاديمية
أعرض في EDS

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway.

التفاصيل البيبلوغرافية
العنوان: LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-β signalling pathway.
المؤلفون: Yu X; Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China., Huang J; Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, P.R. China., Liu X; College of Pharmacy, Xinxiang Medical University, No. 601 Jin-sui Road, Xinxiang, 453003, Henan, P.R. China.; Henan International Joint Laboratory of Cardiovascular Remodelling and Drug Intervention, Xinxiang, 453003, Henan, P.R. China.; Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, Henan, P.R. China., Li J; Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China., Yu M; College of Pharmacy, Xinxiang Medical University, No. 601 Jin-sui Road, Xinxiang, 453003, Henan, P.R. China.; Henan International Joint Laboratory of Cardiovascular Remodelling and Drug Intervention, Xinxiang, 453003, Henan, P.R. China., Li M; College of Pharmacy, Xinxiang Medical University, No. 601 Jin-sui Road, Xinxiang, 453003, Henan, P.R. China.; Henan International Joint Laboratory of Cardiovascular Remodelling and Drug Intervention, Xinxiang, 453003, Henan, P.R. China., Xie Y; College of Pharmacy, Xinxiang Medical University, No. 601 Jin-sui Road, Xinxiang, 453003, Henan, P.R. China.; Henan International Joint Laboratory of Cardiovascular Remodelling and Drug Intervention, Xinxiang, 453003, Henan, P.R. China., Li Y; The First Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Qiu J; Queen Mary School, Medical Department, Nanchang University, Nanchang, 330031, China., Xu Z; The Second Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Zhu T; College of Pharmacy, Xinxiang Medical University, No. 601 Jin-sui Road, Xinxiang, 453003, Henan, P.R. China. zhutt@xxmu.edu.cn.; Henan International Joint Laboratory of Cardiovascular Remodelling and Drug Intervention, Xinxiang, 453003, Henan, P.R. China. zhutt@xxmu.edu.cn., Zhang W; Department of Pharmacy, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China. z_weifang@163.com.; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China. z_weifang@163.com.
المصدر: Respiratory research [Respir Res] 2024 Jul 10; Vol. 25 (1), pp. 270. Date of Electronic Publication: 2024 Jul 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101090633 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-993X (Electronic) Linking ISSN: 14659921 NLM ISO Abbreviation: Respir Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2001- : London : BioMed Central Ltd.
Original Publication: London : Current Science Ltd., c2000-
مواضيع طبية MeSH: RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , MicroRNAs*/metabolism , MicroRNAs*/genetics , Hypoxia*/metabolism , Hypoxia*/genetics , Rats, Sprague-Dawley* , Signal Transduction*/physiology , Hypertension, Pulmonary*/metabolism , Hypertension, Pulmonary*/genetics , Hypertension, Pulmonary*/pathology , Epithelial-Mesenchymal Transition*/physiology , Epithelial-Mesenchymal Transition*/genetics , Transforming Growth Factor beta*/metabolism, Animals ; Rats ; Humans ; Male ; Female ; Receptor, Transforming Growth Factor-beta Type I/metabolism ; Receptor, Transforming Growth Factor-beta Type I/genetics ; Pulmonary Artery/metabolism ; Pulmonary Artery/pathology ; Disease Models, Animal ; RNA, Competitive Endogenous
مستخلص: Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined.
Methods: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19.
Results: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency.
Conclusions: In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 202310472003 National College Students Innovation Training Program of Henan Province; 20204BCJ23020 the Young Talents Project Foundation from Science and Technology Department of Jiangxi Province; 81960015 National Natural Science Foundation of China
فهرسة مساهمة: Keywords: Endothelial-to-mesenchymal transition; Hypoxic pulmonary hypertension; TGFβR1; lncRNA-H19; microRNA-let-7 g
المشرفين على المادة: 0 (RNA, Long Noncoding)
0 (H19 long non-coding RNA)
0 (MicroRNAs)
0 (Transforming Growth Factor beta)
0 (mirnlet7 microRNA, human)
0 (MIRNLET7 microRNA, rat)
EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
0 (RNA, Competitive Endogenous)
تواريخ الأحداث: Date Created: 20240710 Date Completed: 20240711 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC11238495
DOI: 10.1186/s12931-024-02895-y
PMID: 38987833
قاعدة البيانات: MEDLINE
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