Upregulation of Interleukin-33 in obstructive renal injury

Wei Yu Chen, Ya Jen Chang, Chia Hao Su, Tzu Hsien Tsai, Shang Der Chen, Chung Hsi Hsing, Jenq Lin Yang

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22 Citations (Scopus)

Abstract

Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases.

Original languageEnglish
Pages (from-to)1026-1032
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume473
Issue number4
DOIs
Publication statusPublished - May 13 2016
Externally publishedYes

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Keywords

  • Interleukin-33
  • Obstructive nephropathy
  • Renal fibrosis
  • Tubular cell injury

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Chen, W. Y., Chang, Y. J., Su, C. H., Tsai, T. H., Chen, S. D., Hsing, C. H., & Yang, J. L. (2016). Upregulation of Interleukin-33 in obstructive renal injury. Biochemical and Biophysical Research Communications, 473(4), 1026-1032. https://doi.org/10.1016/j.bbrc.2016.04.010