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Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

التفاصيل البيبلوغرافية
العنوان: Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.
المؤلفون: Yang C; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Sun M; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Yang Y; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.; Department of Anesthesia, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China., Han Y; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Wu X; Institute of Geriatrics, Southwest Hospital, Army Medical University, Chongqing, China., Wu X; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Cao H; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Chen L; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Lei Y; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Hu X; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Chen Y; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Zeng Z; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Li J; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Shu X; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Yang Z; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Lu K; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Li Y; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China., Wang X; MCD, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France., Yi B; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
المصدر: European journal of clinical investigation [Eur J Clin Invest] 2024 Aug; Vol. 54 (8), pp. e14212. Date of Electronic Publication: 2024 Apr 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: England NLM ID: 0245331 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2362 (Electronic) Linking ISSN: 00142972 NLM ISO Abbreviation: Eur J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley
Original Publication: Berlin, New York, Springer-Verlag, on behalf of the European Society for Clinical Investigation.
مواضيع طبية MeSH: Hepatopulmonary Syndrome*/metabolism , Growth Differentiation Factor 2*/metabolism , Signal Transduction* , Activin Receptors, Type II*/metabolism , Lung*/metabolism , Smad1 Protein*/metabolism , Endoglin*/metabolism , Neovascularization, Pathologic*/metabolism, Animals ; Rats ; Male ; Endothelial Cells/metabolism ; Disease Models, Animal ; Smad5 Protein/metabolism ; Rats, Sprague-Dawley ; Cell Proliferation ; Common Bile Duct ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Monocytes/metabolism ; Angiogenesis ; Activin Receptors
مستخلص: Background: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS.
Methods: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells.
Results: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats.
Conclusions: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.
(© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)
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معلومات مُعتمدة: 81870422 National Science Foundation of China; 82070630 National Science Foundation of China; 82100658 National Science Foundation of China; 82270656 National Science Foundation of China; CSTB2022 NSCQ-MSX0218 Natural Science Foundation of Chongqing Municipality; CSTB2023NSCQ-ZDJ0005 Natural Science Foundation of Chongqing Municipality; cstc2019jcyj-msxmX0746 Natural Science Foundation of Chongqing Municipality; CSTB2022BSXM-JCX0006 Natural Science Foundation of Chongqing Municipality; CQYC202103080 Chongqing Science and Technology Innovation Leading Talent Support Program
فهرسة مساهمة: Keywords: activin receptor‐like kinase1; angiogenesis; bone morphogenetic protein 9; common bile duct ligation; hepatopulmonary syndrome; pulmonary microvascular endothelial cells
المشرفين على المادة: 0 (Growth Differentiation Factor 2)
EC 2.7.11.30 (Activin Receptors, Type II)
0 (Smad1 Protein)
0 (Endoglin)
0 (Acvrl1 protein, rat)
0 (Smad5 Protein)
0 (Eng protein, rat)
0 (Smad1 protein, rat)
0 (Smad5 protein, rat)
EC 2.7.11.30 (Activin Receptors)
تواريخ الأحداث: Date Created: 20240409 Date Completed: 20240715 Latest Revision: 20240715
رمز التحديث: 20240715
DOI: 10.1111/eci.14212
PMID: 38591651
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2362
DOI:10.1111/eci.14212