The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment

Thanutchaporn Kumrungsee*, Taishi Kariya, Kotaro Hashimoto, Takayuki Koyano, Nao Yazawa, Takao Hashimoto, Yohei Sanada, Makoto Matsuyama, Yusuke Sotomaru, Hiroaki Sakurai, Fons A.J. van de Loo, Noriyuki Yanaka

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

8 被引用数 (Scopus)

抄録

Tubulointerstitial fibrosis is a progressive process affecting the kidneys, causing renal failure that can be life-threatening. Thus, renal fibrosis has become a serious concern in the ageing population; however, fibrotic development cannot be diagnosed early and assessed noninvasively in both patients and experimental animal models. Here, we found that serum amyloid A3 (Saa3) expression is a potent indicator of early renal fibrosis; we also established in vivo Saa3/C/EBPβ-promoter bioluminescence imaging as a sensitive and specific tool for early detection and visualization of tubulointerstitial fibrosis. Saa3 promoter activity is specifically upregulated in parallel with tumor necrosis factor α (TNF-α) and fibrotic marker collagen I in injured kidneys. C/EBPβ, upregulated in injured kidneys and expressed in tubular epithelial cells, is essential for the increased Saa3 promoter activity in response to TNF-α, suggesting that C/EBPβ plays a crucial role in renal fibrosis development. Our model successfully enabled visualization of the suppressive effects of a citrus flavonoid derivative, glucosyl-hesperidin, on inflammation and fibrosis in kidney disease, indicating that this model could be widely used in exploring therapeutic agents for fibrotic diseases.

本文言語英語
論文番号14101
ジャーナルScientific Reports
9
1
DOI
出版ステータス出版済み - 2019/12/01

ASJC Scopus 主題領域

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