Abstract
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.
Highlights
About 750 million people suffer from chronic kidney disease (CKD) with global deaths predicted to rise from 1.2 million in 2016 to 3.1 million in 20401,2
CCAAT/ enhancer binding protein β (C/EBPβ) is transcriptionally activated by inflammatory stimuli, including inflammatory cytokines, such as interleukin-6 (IL-6), IL-1, and tumor necrosis factor α (TNF-α), and the possibility that C/EBPβ may play an important role in inflammatory signals during disease development has been explored[12,13,17,18,19]
These observations indicate that C/EBPβ and its regulated Saa family of genes may represent an important target for assessing kidney injury and the serum amyloid A3 (Saa3)-promoter reporter might be used in live animals for visualizing the injury in experimental kidney disease models and for monitoring therapeutic effects of functional food on the pathology of diseases
Summary
About 750 million people suffer from chronic kidney disease (CKD) with global deaths predicted to rise from 1.2 million in 2016 to 3.1 million in 20401,2. There is an upregulation of the Saa family proteins in serum and kidney tissue of both patients and experimental animals having kidney disease[20,21,22,23,24,25] Taken together, these observations indicate that C/EBPβ and its regulated Saa family of genes may represent an important target for assessing kidney injury and the Saa3-promoter reporter might be used in live animals for visualizing the injury in experimental kidney disease models and for monitoring therapeutic effects of functional food on the pathology of diseases. We report that in vivo Saa3/C/EBPβ-promoter bioluminescence imaging is a novel, sensitive, and specific approach for detecting and visualizing tubulointerstitial injury and fibrosis as well as monitoring the therapeutic effect of functional food on kidney disease. As C/EBPβ is likely to be an upstream regulator for tubulointerstitial fibrosis, our finding may open the door to the design of future therapeutic strategies or screening for novel therapeutic functional food by controlling the levels of expression of C/EBPβ
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
