論文

国際誌
2021年11月4日

TGF-β1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction.

Scientific reports
  • Sayo Ueda
  • ,
  • Tatsuya Tominaga
  • ,
  • Arisa Ochi
  • ,
  • Akiko Sakurai
  • ,
  • Kenji Nishimura
  • ,
  • Eriko Shibata
  • ,
  • Shu Wakino
  • ,
  • Masanori Tamaki
  • ,
  • Kojiro Nagai

11
1
開始ページ
21643
終了ページ
21643
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-021-01150-4

p16 inhibits cyclin-dependent kinases and regulates senescence-mediated arrest as well as p21. Nuclear p16 promotes G1 cell cycle arrest and cellular senescence. In various glomerular diseases, nuclear p16 expression is associated with disease progression. Therefore, the location of p16 is important. However, the mechanism of p16 trafficking between the nucleus and cytoplasm is yet to be fully investigated. TGF-β1, a major cytokine involved in the development of kidney diseases, can upregulate p21 expression. However, the relationship between TGF-β1 and p16 is poorly understood. Here, we report the role of podocyte TGF-β1 in regulating the p16 behavior in glomerular endothelial cells. We analyzed podocyte-specific TGF-β1 overexpression mice. Although p16 was found in the nuclei of glomerular endothelial cells and led to endothelial cellular senescence, the expression of p16 did not increase in glomeruli. In cultured endothelial cells, TGF-β1 induced nuclear translocation of p16 without increasing its expression. Among human glomerular diseases, p16 was detected in the nuclei of glomerular endothelial cells. In summary, we demonstrated the novel role of podocyte TGF-β1 in managing p16 behavior and cellular senescence in glomeruli, which has clinical relevance for the progression of human glomerular diseases.

リンク情報
DOI
https://doi.org/10.1038/s41598-021-01150-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34737348
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569175
ID情報
  • DOI : 10.1038/s41598-021-01150-4
  • PubMed ID : 34737348
  • PubMed Central 記事ID : PMC8569175

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