Original Articles
30 August 2023
Vol. 17 No. 2 (2023)
Smad2/3 signaling involved in urotensin II-induced phenotypic differentiation, collagen synthesis and migration of rat aortic adventitial fibroblasts
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
790
Views
374
Downloads
21
HTML
Authors
Objective. To investigate whether Smad2/3 signaling is involved in urotensin II (UII) induced activation of aortic adventitial fibroblasts. Materials and Methods. Growth-arrested adventitial fibroblasts were stimulated with UII in the presence or absence of urotensin II receptor (UT) antagonist SB710411 or transfected with Smad2/3 small inhibitory RNA (siRNA). UII stimulated Smad2/3 phosphorylation, α-smooth muscle actin (α-SMA), and collagen I expression and migration of adventitial fibroblasts were evaluated by western blot analysis, real-time reverse transcription polymerase chain reaction, immunofluorescence, ELISA, and transwell migration assay, respectively. Results. In cultured adventitial fibroblasts, UII time- and dose-dependently stimulated Smad2/3 protein phosphorylation, with maximal effect at 10-8 mol/l (increased by 147.2%, P<0.001). UII stimulated Smad2/3 upregulation and nuclear translocation. SB710411 significantly inhibited these effects. In addition, UII potently induced α-SMA and procollagen 1 protein or mRNA expression (P<0.01), which were completely blocked by Smad2 (decreased by 75.1%, 54.2% in protein, and by 73.3% and 38.2% in mRNA, respectively, P<0.01) or Smad3 siRNA (decreased by 80.3% and 47.0% in protein, and by 72.3% and 47.7% in mRNA, respectively, P<0.01). Meanwhile, Smad2 or smad3 siRNA significantly inhibited the UII-induced collagen 1 secretion and cell migration. Conclusions. UII may stimulate adventitial-fibroblast phenotype conversion, migration, and collagen I synthesis via phosphorylated-Smad2/3 signal transduction pathways.
Altmetrics
Downloads
Download data is not yet available.
Citations
Rodriguez-Vita J, Sanchez-Lopez E, Esteban V, et al. Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factorbeta-independent mechanism. Circulation 2005;111:2509-17. DOI: https://doi.org/10.1161/01.CIR.0000165133.84978.E2
Liu Y, Liang C, Liu X, et al. AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways. Atherosclerosis 2010;208:34-42. DOI: https://doi.org/10.1016/j.atherosclerosis.2009.06.007
Lan TH, Huang XQ, Tan HM. Vascular fibrosis in atherosclerosis. Cardiovasc Pathol 2013;22:401-7. DOI: https://doi.org/10.1016/j.carpath.2013.01.003
Stenmark KR, Yeager ME, El KK, et al. The adventitia: essential regulator of vascular wall structure and function. Annu Rev Physiol 2013;75:23-47. DOI: https://doi.org/10.1146/annurev-physiol-030212-183802
Wu X, Lu Q. Expression and significance of alpha-SMA and PCNA in the vascular adventitia of balloon-injured rat aorta. Exp Ther Med 2013;5:1671-6. DOI: https://doi.org/10.3892/etm.2013.1059
Evans RA, Tian YC, Steadman R, Phillips AO. TGFbeta1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp Cell Res 2003;282:90-100. DOI: https://doi.org/10.1016/S0014-4827(02)00015-0
Forte A, Della CA, De Feo M, et al. Role of myofibroblasts in vascular remodelling: focus on restenosis and aneurysm. Cardiovasc Res 2010;88:395-405. DOI: https://doi.org/10.1093/cvr/cvq224
Boyd R, Ratsep MT, Ding LL, Wang HD. ETA and ETB receptors are expressed in vascular adventitial fibroblasts. Am J Physiol Heart Circ Physiol 2011;301:H2271-H2278. DOI: https://doi.org/10.1152/ajpheart.00869.2010
Song N, Ding W, Chu S, et al. Urotensin II stimulates vascular endothelial growth factor secretion from adventitial fibroblasts in synergy with angiotensin II. Circ J 2012;76:1267-73. DOI: https://doi.org/10.1253/circj.CJ-11-0870
Zhang YG, Hu YC, Mao YY, et al. Transforming growth factor-beta1 involved in urotensin II-induced phenotypic differentiation of adventitial fibroblasts from rat aorta. Chin Med J (Engl) 2010;123:3634-9.
Di Wang H, Ratsep MT, Chapman A, Boyd R. Adventitial fibroblasts in vascular structure and function. the role of oxidative stress and beyond. Can J Physiol Pharmacol 2010;88:177-86. DOI: https://doi.org/10.1139/Y10-015
Zhang YG, Li YG, Wei RH, et al. Urotensin II is an autocrine/paracrine growth factor for aortic adventitia of rat. Regul Pept 2008;151:88-94. DOI: https://doi.org/10.1016/j.regpep.2008.10.004
Shi L, Ding W, Li D, et al. Proliferation and anti-apoptotic effects of human urotensin II on human endothelial cells. Atherosclerosis 2006;188:260-4. DOI: https://doi.org/10.1016/j.atherosclerosis.2005.10.044
Vaudry H, Leprince J, Chatenet D, et al. International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function. Pharmacol Rev 2015;67:214-58. DOI: https://doi.org/10.1124/pr.114.009480
Zhang YG, Li J, Li YG, Wei RH. Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta. J Hypertens 2008;26:1119-26. DOI: https://doi.org/10.1097/HJH.0b013e3282fa1412
Shiraishi Y, Watanabe T, Suguro T, et al. Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein Eknockout mice. J Hypertens 2008;26:1955-65. DOI: https://doi.org/10.1097/HJH.0b013e32830b61d8
Zhao J, Ding W, Song N, et al. Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-beta1/Smad2/3 signaling pathway. Regul Pept 2013;182:53-8. DOI: https://doi.org/10.1016/j.regpep.2012.12.006
Tzanidis A, Hannan RD, Thomas WG, et al. Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res 2003;93:246-53. DOI: https://doi.org/10.1161/01.RES.0000084382.64418.BC
Wang W, Huang XR, Canlas E, et al. Essential role of Smad3 in angiotensin II-induced vascular fibrosis. Circ Res 2006;98:1032-9. DOI: https://doi.org/10.1161/01.RES.0000218782.52610.dc
Rodrigues DR, Rodrigues-Diez R, Lavoz C, et al. Statins inhibit angiotensin II/Smad pathway and related vascular fibrosis, by a TGF-beta-independent process. PLoS One 2010;5:e14145. DOI: https://doi.org/10.1371/journal.pone.0014145
Javelaud D, Mauviel A. Mammalian transforming growth factor-betas: Smad signaling and physio-pathological roles. Int J Biochem Cell Biol 2004;36:1161-5. DOI: https://doi.org/10.1016/S1357-2725(03)00255-3
Yang F, Chung AC, Huang XR, Lan HY. Angiotensin II induces connective tissue growth factor and collagen I expression via transforming growth factor-beta-dependent and -independent Smad pathways: the role of Smad3. Hypertension 2009;54:877-84. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.109.136531
Li JH, Huang XR, Zhu HJ, et al. Advanced glycation end products activate Smad signaling via TGF-betadependent and independent mechanisms: implications for diabetic renal and vascular disease. FASEB J 2004;18:176-8. DOI: https://doi.org/10.1096/fj.02-1117fje
Dai HY, Kang WQ, Wang X, et al. The involvement of transforming growth factor-beta1 secretion in urotensin II-induced collagen synthesis in neonatal cardiac fibroblasts. Regul Pept 2007;140:88-93. DOI: https://doi.org/10.1016/j.regpep.2006.11.015
Tran L, Kompa AR, Kemp W, et al. Chronic urotensin-II infusion induces diastolic dysfunction and enhances collagen production in rats. Am J Physiol Heart Circ Physiol 2010;298:H608-H613. DOI: https://doi.org/10.1152/ajpheart.00942.2009
Matsusaka S, Wakabayashi I. Enhancement of vascular smooth muscle cell migration by urotensin II. Naunyn Schmiedebergs Arch Pharmacol 2006;373:381-6. DOI: https://doi.org/10.1007/s00210-006-0086-x
Xu S, Jiang H, Wu B, et al. Urotensin II induces migration of endothelial progenitor cells via activation of the RhoA/Rho kinase pathway. Tohoku J Exp Med 2009;219:283-388. DOI: https://doi.org/10.1620/tjem.219.283
Zhang YG, Kuang ZJ, Mao YY, et al. Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts. Peptides 2011;32:2452-8. DOI: https://doi.org/10.1016/j.peptides.2011.10.018
Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 2007;127:526-37. DOI: https://doi.org/10.1038/sj.jid.5700613
Desmouliere A, Darby IA, Gabbiani G. Normal and pathologic soft tissue remodeling. role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 2003;83:1689-707. DOI: https://doi.org/10.1097/01.LAB.0000101911.53973.90
Supporting Agencies
National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province of ChinaHow to Cite
Smad2/3 signaling involved in urotensin II-induced phenotypic differentiation, collagen synthesis and migration of rat aortic adventitial fibroblasts. (2023). Italian Journal of Medicine, 17(2). https://doi.org/10.4081/itjm.2023.1637
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Giulia Bombardieri, Alessandra Rustici, Michele Caselli, Chiara Chirico, Veronica Bocchi, Andrea Montagnani, Segmental arterial mediolysis: a challenging diagnosis in internal medicine , Italian Journal of Medicine: Vol. 18 No. 3 (2024)
- Pietro Crispino, Luca Fontanella, Paola Gnerre, Liver diseases and pregnancy , Italian Journal of Medicine: Vol. 11 No. 3 (2017)
- Fernando Gallucci, Ilaria Ronga, Francesco Di Pietto, Gerardino Amato, Rosario Buono, Generoso Uomo, Adult bacterial myositis: report of a single-center series of 26 cases , Italian Journal of Medicine: Vol. 10 No. 3 (2016)
- Aurelio Negro, Rosaria Santi, Chiara Grasselli, Simona Davoli, Franco Perazzoli, A case of posterior reversible encephalopathy syndrome in the setting of post-partum preeclampsia with suppressed plasma aldosterone levels and plasma renin activity , Italian Journal of Medicine: Vol. 7 No. 4 (2013)
- Daniela Tirotta, Vittorio Durante, Problem-solving combined with ultrasonography: a strategy for internists to improve case management and reduce diagnostic errors , Italian Journal of Medicine: Vol. 8 No. 1 (2014)
- Flavio Cursi, Folate deficiency and psycho-organic syndrome in elderly subjects: review of the literature , Italian Journal of Medicine: Vol. 12 No. 2 (2018)
- Riccardo Gerloni, Luciano Mucci, Carlotta Casati, Andrea Crociani, Ombretta Para, Elisabetta Benetti, Paola Gnerre, Anna Bovero, Elisa Romagnoli, Nicola Tarquinio, Clelia Canale, Davide Brancato, Laura Massarelli, Salvatora Piras, Management of sepsis: from evidence to clinical practice , Italian Journal of Medicine: Vol. 10 No. 4 (2016)
- Bui Quang Huynh, Nguyen Duy Hung, Le Thanh Dung, Nguyen-Thi Thu, Nguyen-Thi Hai Anh, Ngo Quang Duy, Nguyen Minh Duc, The value of computed tomography perfusion for assessing the response of hepatocellular carcinoma to transarterial chemoembolization , Italian Journal of Medicine: Vol. 18 No. 3 (2024)
- Michele Meschi, Simona Detrenis, Laura Bianchi, Marcella Saccò, Marcello Bertorelli, Sarah Pioli, Francesca Boffetti, Francesca Spagnoli, Enrico Fiaccadori, Alberto Caiazza, Hypertension and emergency medicine: an update , Italian Journal of Medicine: Vol. 7 No. 1 (2013)
- Cecilia Politi, Tiziana Ciarambino, Flavia Franconi, Lucrezia De Feudis, Maria Carolina Mayer, Alessandra Martignoni, Ilaria Giovi, Michela Tonani, Salvatore La Carrubba, Anna Maria Moretti, Carmen Martino, Giovanni Scanelli, Gender medicine: an up-date , Italian Journal of Medicine: Vol. 7 No. 2 (2013)
You may also start an advanced similarity search for this article.