IL-33/ST2 axis mediates hyperplasia of intrarenal urothelium in obstructive renal injury

Wei Yu Chen, Jenq Lin Yang, Yi Hsiu Wu, Lung Chih Li, Ru Fang Li, Ya Ting Chang, Lo Hsin Dai, Wan Chen Wang, Ya Jen Chang

研究成果: Article同行評審

16 引文 斯高帕斯(Scopus)

摘要

The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5-positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.

原文English
文章編號36
期刊Experimental and Molecular Medicine
50
發行號4
DOIs
出版狀態Published - 2018 4月 1

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 分子醫學
  • 分子生物學
  • 臨床生物化學

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