| RRC ID |
85011
|
| 著者 |
Kurawaki S, Nakashima A, Ishiuchi N, Kanai R, Maeda S, Sasaki K, Masaki T.
|
| タイトル |
Mesenchymal stem cells pretreated with interferon-gamma attenuate renal fibrosis by enhancing regulatory T cell induction.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Mesenchymal stem cells (MSCs) exert their anti-inflammatory and anti-fibrotic effects by secreting various humoral factors. Interferon-gamma (IFN-γ) can enhance these effects of MSCs, and enhancement of regulatory T (Treg) cell induction is thought to be an underlying mechanism. However, the extent to which Treg cell induction by MSCs pretreated with IFN-γ (IFN-γ MSCs) ameliorates renal fibrosis remains unknown. In this study, we investigated the effects of Treg cell induction by IFN-γ MSCs on renal inflammation and fibrosis using an siRNA knockdown system. Administration of IFN-γ MSCs induced Treg cells and inhibited infiltration of inflammatory cells in ischemia reperfusion injury (IRI) rats more drastically than control MSCs without IFN-γ pretreatment. In addition, administration of IFN-γ MSCs more significantly attenuated renal fibrosis compared with control MSCs. Indoleamine 2,3-dioxygenase (IDO) expression levels in conditioned medium from MSCs were enhanced by IFN-γ pretreatment. Moreover, IDO1 knockdown in IFN-γ MSCs reduced their anti-inflammatory and anti-fibrotic effects in IRI rats by reducing Treg cell induction. Our findings suggest that the increase of Treg cells induced by enhanced secretion of IDO by IFN-γ MSCs played a pivotal role in their anti-fibrotic effects. Administration of IFN-γ MSCs may potentially be a useful therapy to prevent renal fibrosis progression.
|
| 巻・号 |
14(1)
|
| ページ |
10251
|
| 公開日 |
2024-5-4
|
| DOI |
10.1038/s41598-024-60928-4
|
| PII |
10.1038/s41598-024-60928-4
|
| PMID |
38704512
|
| PMC |
PMC11069572
|
| MeSH |
Animals
Fibrosis*
Indoleamine-Pyrrole 2,3,-Dioxygenase* / metabolism
Interferon-gamma* / metabolism
Kidney / drug effects
Kidney / pathology
Kidney Diseases / pathology
Kidney Diseases / therapy
Male
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells* / metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury / immunology
T-Lymphocytes, Regulatory* / immunology
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
Human MSCs |
