| First Author | Wu Y | Year | 2023 |
| Journal | Cells | Volume | 12 |
| Issue | 2 | PubMed ID | 36672147 |
| Mgi Jnum | J:352159 | Mgi Id | MGI:7429448 |
| Doi | 10.3390/cells12020214 | Citation | Wu Y, et al. (2023) Notch Blockade Specifically in Bone Marrow-Derived FSP-1-Positive Cells Ameliorates Renal Fibrosis. Cells 12(2) |
| abstractText | BACKGROUND: The infiltration of inflammatory cells during a kidney injury stimulates myofibroblast activation leading to kidney fibrosis. Fibroblast-specific protein 1 (FSP-1) positive cells have been reported as either myofibroblasts or monocytes during tissue fibrosis. The functions of FSP-1(+) cells that are associated with the development of renal fibrosis and the signaling pathways that regulate FSP-1(+) cell activation have not been well defined. METHODS: In mice with unilateral ureteral obstruction (UUO), we characterized FSP-1(+) cells and determined the role of the Notch signaling pathway in the activation of bone marrow-derived FSP-1(+) cells during kidney fibrosis. RESULTS: In kidneys from mice with UUO, the FSP-1(+) cells accumulated significantly in the tubulointerstitial area. By using immunostaining and FSP-1 reporter mice, we found that FSP-1 was co-stained with inflammatory cell markers, but not myofibroblast markers. Results from mice with bone marrow transplantations showed that FSP-1(+) cells in obstructed kidneys represent a bone marrow-derived population of inflammatory cells. In cultured FSP-1(+) cells, the inhibition of Notch signaling suppressed the activation and cytokine secretion of FSP-1(+) cells that were induced by LPS but not by IL-4. The specific KO or blockade of Notch signaling in bone marrow-derived FSP-1(+) cells suppressed UUO-induced ECM deposition, the infiltration of FSP-1(+) inflammatory cells, and cytokine production. These responses ameliorated myofibroblast accumulation and renal fibrosis in obstructed kidneys. CONCLUSION: Our study reveals that most FSP-1(+) cells in obstructed kidneys are activated macrophages that are derived from bone marrow and that Notch signaling activates the production of M1 cytokines in FSP-1(+) monocytes/macrophages, which is important for renal inflammation and fibrosis. |
