Back to Search
Start Over
Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis.
- Source :
-
Scientific reports [Sci Rep] 2021 Jan 13; Vol. 11 (1), pp. 850. Date of Electronic Publication: 2021 Jan 13. - Publication Year :
- 2021
-
Abstract
- Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs' therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia-reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.
- Subjects :
- Animals
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Cells, Cultured
Culture Media, Conditioned
Dinoprostone metabolism
Fibrosis therapy
Kidney pathology
Kidney Diseases drug therapy
Killer Cells, Natural metabolism
Macrophages metabolism
Male
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface metabolism
Reperfusion Injury physiopathology
Reperfusion Injury therapy
Ureteral Obstruction physiopathology
Ureteral Obstruction therapy
Interferon-gamma pharmacology
Kidney Diseases therapy
Mesenchymal Stem Cell Transplantation methods
Mesenchymal Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33441701
- Full Text :
- https://doi.org/10.1038/s41598-020-79664-6