دورية أكاديمية
Apelin-13: a novel approach to suppressing renin production in RVHT.
| العنوان: | Apelin-13: a novel approach to suppressing renin production in RVHT. |
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| المؤلفون: | Yan Z; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Yang T; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Li X; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Jiang Z; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Jia W; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Zhou J; School of PharmacyWeifang Medical University, Weifang, Shandong, China., Fang H; School of PharmacyWeifang Medical University, Weifang, Shandong, China. |
| المصدر: | American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2024 Jun 01; Vol. 326 (6), pp. C1683-C1696. Date of Electronic Publication: 2024 Apr 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1563 (Electronic) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, Md. : American Physiological Society, |
| مواضيع طبية MeSH: | Renin*/metabolism , Renin*/genetics , Rats, Sprague-Dawley* , Intercellular Signaling Peptides and Proteins*/metabolism , Intercellular Signaling Peptides and Proteins*/genetics , Hypertension, Renovascular*/metabolism , Hypertension, Renovascular*/drug therapy , Hypertension, Renovascular*/genetics, Animals ; Male ; Rats ; Humans ; Mice ; Renin-Angiotensin System/drug effects ; Kidney/metabolism ; Prorenin Receptor ; Angiotensin II/metabolism ; Cyclic AMP/metabolism ; Blood Pressure/drug effects ; Signal Transduction ; Cell Line ; Disease Models, Animal ; Cyclic AMP Response Element-Binding Protein/metabolism |
| مستخلص: | Renovascular hypertension (RVHT) is characterized by renal artery stenosis and overactivated renin-angiotensin system (RAS). Apelin, known for its negative modulation of RAS, has protective effects against cardiovascular diseases. The role and mechanisms of the primary active form of apelin, apelin-13, in RVHT are unclear. In this study, male Sprague-Dawley rats were divided into control, two-kidney one-clip (2K1C) model, and 2K1C with apelin-13 treatment groups. Renin expression was analyzed using immunohistochemistry and molecular techniques. Full-length (pro)renin receptor (fPRR) and soluble PRR (sPRR) levels were assessed via Western blotting, and cAMP levels were measured using ELISA. Plasma renin content, plasma renin activity (PRA), angiotensin II (ANG II), and sPRR levels were determined by ELISA. Human Calu-6 and mouse As4.1 cells were used to investigate renin production mechanisms. The 2K1C model exhibited increased systolic blood pressure, plasma renin content, PRA, sPRR, and ANG II levels, while apelin-13 treatment reduced these elevations. Apelin-13 inhibited cAMP production, renin mRNA expression, protein synthesis, and PRR/sPRR protein expression in renal tissue. In Calu-6 cells, cAMP-induced fPRR and site-1 protease (S1P)-derived sPRR expression, which was blocked by cAMP-responsive element-binding protein (CREB) inhibition. Apelin-13 suppressed cAMP elevation, CREB phosphorylation, fPRR/sPRR protein expression, and renin production. Recombinant sPRR (sPRR-His) stimulated renin production, which was inhibited by the PRR decoy peptide PRO20 and S1P inhibitor PF429242. These findings suggest that apelin-13 inhibits plasma renin expression through the cAMP/PKA/sPRR pathway, providing a potential therapeutic approach for RVHT. Understanding the regulation of renin production is crucial for developing effective treatments. NEW & NOTEWORTHY Our research elucidated that apelin-13 inhibits renin production through the cAMP/PKA/soluble (pro)renin receptor pathway, presenting a promising therapeutic approach for renovascular hypertension (RVHT) by targeting renin expression mechanisms. These findings underscore the potential of apelin-13 as a novel strategy to address RVHT. |
| معلومات مُعتمدة: | 82000400 MOST | National Natural Science Foundation of China (NSFC); 2021YX043 Weifang Science and Technology Development Plan |
| فهرسة مساهمة: | Keywords: apelin-13; cAMP; juxtaglomerular cells; renovascular hypertension; soluble (pro)renin receptor |
| المشرفين على المادة: | EC 3.4.23.15 (Renin) 0 (apelin-13 peptide) 0 (Intercellular Signaling Peptides and Proteins) 0 (Prorenin Receptor) 11128-99-7 (Angiotensin II) E0399OZS9N (Cyclic AMP) 0 (Cyclic AMP Response Element-Binding Protein) |
| تواريخ الأحداث: | Date Created: 20240422 Date Completed: 20240606 Latest Revision: 20240617 |
| رمز التحديث: | 20240617 |
| DOI: | 10.1152/ajpcell.00092.2024 |
| PMID: | 38646785 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1563 |
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| DOI: | 10.1152/ajpcell.00092.2024 |