https://doi.org/10.4081/itjm.2023.1637

Smad2/3 signaling involved in urotensin II-induced phenotypic differentiation, collagen synthesis and migration of rat aortic adventitial fibroblasts

Vol. 17 No. 2 (2023)
Published: 30 August 2023
Urotensin II, adventitial fibroblasts, Smad, signal transduction, vascular fibrosis
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Authors

Weizhao Lin
Department of Cardiology, Second Affiliated Hospital, Shantou University Medical College, Shantou; Cardiovascular Laboratory, Centre for Translational Medicine, Shantou University Medical College, Shantou, China.
Xu Yang
Department of Cardiology, Second Affiliated Hospital, Shantou University Medical College, Shantou; Cardiovascular Laboratory, Centre for Translational Medicine, Shantou University Medical College, Shantou, China.
Fan Zheng
Department of Cardiology, Second Affiliated Hospital, Shantou University Medical College, Shantou; Cardiovascular Laboratory, Centre for Translational Medicine, Shantou University Medical College, Shantou, China.
Jianshe Yang
yangjs@impcas.ac.cn
https://orcid.org/0000-0001-7069-6072
Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China.
Yonggang Zhang
https://orcid.org/0000-0003-2650-5309
Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China.

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.

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Supporting Agencies

National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province of China

How to Cite

Lin, W., Yang, X., Zheng, F., Yang, J., & Zhang, Y. (2023). Smad2/3 signaling involved in urotensin II-induced phenotypic differentiation, collagen synthesis and migration of rat aortic adventitial fibroblasts. Italian Journal of Medicine, 17(2). https://doi.org/10.4081/itjm.2023.1637
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