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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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Inhibition of the Semaphorin 4D-Plexin-B1 axis prevents calcification in vascular smooth muscle cells

  • Hyun-Joo Park (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Yeon Kim (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Mi-Kyoung Kim (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Hyung Joon Kim (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Soo-Kyung Bae (Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University) ;
  • Moon-Kyoung Bae (Department of Oral Physiology, School of Dentistry, Pusan National University)
  • 투고 : 2022.10.20
  • 심사 : 2022.11.26
  • 발행 : 2023.03.31
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초록

Vascular calcification is common in cardiovascular diseases including atherosclerosis, and is associated with an increased risk of pathological events and mortality. Some semaphorin family members play an important role in atherosclerosis. In the present study, we show that Semaphorin 4D/Sema4D and its Plexin-B1 receptor were significantly upregulated in calcified aorta of a rat chronic kidney disease model. Significantly higher Sema4D and Plexin-B1 expression was also observed during inorganic phosphate-induced calcification of vascular smooth muscle cells. Knockdown of Sema4D or Plexin-B1 genes attenuated both the phosphate-induced osteogenic phenotype of vascular smooth muscle cells, through regulation of SMAD1/5 signaling, as well as apoptosis of vascular smooth muscle cells, through modulation of the Gas6/Axl/Akt survival pathway. Taken together, our results offer new insights on the role of Sema4D and Plexin-B1 as potential therapeutic targets against vascular calcification.

키워드

과제정보

This research was supported by grants from the National Research Foundation of Korea funded by the Korean government (MSIT, NRF-2018R1A5A2023879 and 2021R1A2C1003687).

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