Abstract | BACKGROUND: Transforming growth factor-β1 (TGF-β1) is a profibrotic cytokine which induces mesothelial cell mesothelial-to-mesenchymal transition ( MMT) and peritoneal fibrosis in patients receiving treatment of peritoneal dialysis. Because thrombospondin-1 (TSP-1) is able to activate latent TGF-β1 in vivo, we investigated whether blockade of TSP-1 could modulate mesothelial cell MMT and ameliorate peritoneal fibrosis. METHODS: RESULTS: Exposure of Met-5A cells to TSP-1 increased TGF-β1 secretion, expression and bioactivity, triggered Smad3 phosphorylation, upregulated the expression of mesenchymal molecules including fibronectin, collagen type III, α-smooth muscle actin, Snail, and decreased calretinin expression. The effect was partially attenuated by TGF-β1 neutralizing antibody. TSP-1 expression in Met-5A cells was increased by 4.25% d-glucose, followed by increased secretion and bioactivity of TGF-β1, the onset of Smad3 phosphorylation and induction of MMT. LSKL significantly attenuated high glucose-mediated mesothelial cell MMT and ameliorated peritoneal fibrosis in uremic rats receiving dextrose dialysate injection. CONCLUSIONS: Taken together, these data demonstrated that TSP-1 contributes to mesothelial cell MMT by activating TGF-β1/Smad3 signaling pathway and blockade of TSP-1 attenuates high glucose-mediated mesothelial cell MMT and peritoneal fibrosis.
|
Authors | Na Jiang, Zhen Zhang, Xinghua Shao, Ran Jing, Chunlin Wang, Wei Fang, Shan Mou, Zhaohui Ni |
Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 235
Issue 1
Pg. 364-379
(01 2020)
ISSN: 1097-4652 [Electronic] United States |
PMID | 31236971
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2019 Wiley Periodicals, Inc. |
Chemical References |
- Antibodies, Neutralizing
- SMAD3 protein, human
- Smad3 Protein
- TGFB1 protein, human
- Thrombospondin 1
- Transforming Growth Factor beta1
- Glucose
|
Topics |
- Animals
- Antibodies, Neutralizing
(pharmacology)
- Cell Differentiation
(physiology)
- Cell Line
- Down-Regulation
(genetics)
- Epithelial Cells
(cytology)
- Glucose
- Humans
- Male
- Peritoneal Dialysis
(adverse effects)
- Peritoneal Fibrosis
(chemically induced, genetics, pathology)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(physiology)
- Smad3 Protein
(metabolism)
- Thrombospondin 1
(antagonists & inhibitors)
- Transforming Growth Factor beta1
(metabolism)
|