Correlation Engine 2.0
Clear Search sequence regions

  • catalysis (1)
  • d (1)
  • dialysis (2)
  • E cadherin (1)
  • fibronectin (1)
  • fingolimod (5)
  • humans (1)
  • lysophospholipids (2)
  • mice (1)
  • patients (1)
  • peritoneal fibrosis (8)
  • research (1)
  • S1P (14)
  • s1p receptor (6)
  • S1PR3 (1)
  • signals (1)
  • sphingolipid (1)
  • SPHK (1)
  • SPHK 1 (9)
  • vimentin (1)
  • Sizes of these terms reflect their relevance to your search.

    Long-term exposure to non-physiologically compatible dialysate inevitably leads to peritoneal fibrosis (PF) in patients undergoing peritoneal dialysis (PD), and there is no effective prevention or treatment for PF. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced after catalysis by sphingosine kinase (SPHK) 1/2 and activates signals through the S1P receptor (S1PR) via autocrine or paracrine. However, the role of SPHK1/S1P/S1PR signaling has never been elucidated in PF. In our research, we investigated S1P levels in peritoneal effluents and demonstrated the role of SPHK1/S1P/S1PR pathway in peritoneal fibrosis. It was found that S1P levels in peritoneal effluents were positively correlated with D/P Cr (r = 0.724, p < .001) and negatively correlated with 4 h ultrafiltration volume (r = -0.457, p < .001). S1PR1 and S1PR3 on peritoneal cells were increased after high glucose exposure in vivo and in vitro. Fingolimod was applied to suppress S1P/S1PR pathway. Fingolimod restored mouse peritoneal function by reducing interstitial hyperplasia, maintaining ultrafiltration volume, reducing peritoneal transport solute rate, and mitigating the protein expression changes of fibronectin, vimentin, α-SMA, and E-cadherin induced by PD and S1P. Fingolimod preserved the morphology of the human peritoneal mesothelial cells, MeT-5A, and moderated the mesothelial-mesenchymal transition (MMT) process. We further delineated that SPHK1 was elevated in peritoneal cells after high glucose exposure and suppression of SPHK1 in MeT-5A cells reduced S1P release. Overexpression of SPHK1 in MeT-5A cells increased S1P levels in the supernatant and fostered the MMT process. PF-543 treatment, targeting SPHK1, alleviated deterioration of mouse peritoneal function. In conclusion, S1P levels in peritoneal effluent were correlated with the deterioration of peritoneal function. SPHK1/S1P/S1PR pathway played an important role in PF. © 2024 Federation of American Societies for Experimental Biology.


    Tingting Zhao, Tao Ding, Zhengyu Sun, Xin Shao, Shuangxi Li, Hongtao Lu, Ji-Hang Yuan, Zhiyong Guo. SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial-mesenchymal transition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2024 Jan 31;38(2):e23417

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 38226856

    View Full Text