دورية أكاديمية
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Targeting serotonin receptor 2B inhibits TGFβ induced differentiation of human vascular smooth muscle cells.

التفاصيل البيبلوغرافية
العنوان: Targeting serotonin receptor 2B inhibits TGFβ induced differentiation of human vascular smooth muscle cells.
المؤلفون: Wenglén C; ANAMAR, Lund, Sweden., Demirel I; Faculty of Medicine and Health, Örebro University, Örebro, Sweden., Eremo AG; Department of Clinical Research Laboratory, Faculty of Medicine, and Health, Örebro University, Örebro, Sweden., Grenegård M; Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden., Paramel GV; Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden. Electronic address: geena.paramel@oru.se.
المصدر: European journal of pharmacology [Eur J Pharmacol] 2023 Apr 05; Vol. 944, pp. 175570. Date of Electronic Publication: 2023 Feb 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2005- : Amsterdam : Elsevier Science
Original Publication: Amsterdam, North Holland Pub. Co.
مواضيع طبية MeSH: Atherosclerosis*/pathology , Transforming Growth Factor beta*/metabolism, Humans ; Carrier Proteins/metabolism ; Cell Differentiation ; Cells, Cultured ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle/metabolism ; Receptor, Serotonin, 5-HT2B/metabolism ; Transforming Growth Factor beta1/metabolism
مستخلص: Vascular Smooth Muscle Cells (VSMCs) are known to be the key drivers of intimal thickening which contribute to early progression of atherosclerosis. VSMCs are the major producers of extracellular matrix within the vessel wall and in response to atherogenic stimuli they could modify the type of matrix proteins produced. Serotonin receptor 2B (5-HT 2B receptor/HTR2B) has been implicated in several chronic fibrotic and vascular diseases. Although studies have successfully demonstrated the efficacy of HTR2B blockade in attenuating fibrotic disease, the role of 5-HT2B receptor in TGFβ mediated VSMC differentiation remain largely unknown. In the present study, we investigated the potential of targeting the 5-HT2B receptor to prevent TGFβ induced VSMCs differentiation. Our results showed that 5-HT2B receptors are expressed in human atherosclerotic lesion and HTR2B expression positively correlated to the VSMCs markers. We show that AM1125, a selective 5-HT2B receptor inhibitor, significantly inhibits TGFβ1 induced production of collagen and CTGF. The investigation of underlying mechanisms indicated that 5-HT2B receptor antagonism blocks phospho-Smad2 mediated downstream signaling of TGFβ1 in vascular smooth muscle cells. Collectively, the HTR2B/TGF-β1/Phospho-Smad2 pathway plays a critical role in the regulation of VSMCs differentiation. Our findings might serve 5-HT2B receptor as a therapeutic target to limit TGF-β1 induced VSMC differentiation.
Competing Interests: Declaration of competing interest C.W. declares employment by AnaMar AB, a company developing 5-HT2B receptor antagonists for therapeutic purposes.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Atherosclerosis; Differentiation; Serotonin receptor; Smad; TGFβ; Vascular smooth muscle cells
المشرفين على المادة: 0 (Carrier Proteins)
0 (Receptor, Serotonin, 5-HT2B)
0 (Transforming Growth Factor beta)
0 (Transforming Growth Factor beta1)
تواريخ الأحداث: Date Created: 20230213 Date Completed: 20230307 Latest Revision: 20230307
رمز التحديث: 20240628
DOI: 10.1016/j.ejphar.2023.175570
PMID: 36781042
قاعدة البيانات: MEDLINE
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