Notch Blockade Specifically in Bone Marrow-Derived FSP-1-Positive Cells Ameliorates Renal Fibrosis

Yongdong Wu, Ming Liang, Fengzhang Huang, Owen H. Cheng, Xiaoguang Xiao, Tae Hoon Lee, Luan Truong, Jizhong Cheng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number214
Issue number2
StatePublished - Jan 4 2023


  • Notch signaling pathway
  • fibroblast specific protein-1 (FSP-1)
  • fibrosis
  • macrophage
  • unilateral ureter obstruction (UUO)
  • S100 Calcium-Binding Protein A4/metabolism
  • Animals
  • Bone Marrow/metabolism
  • Fibrosis
  • Mice
  • Cytokines/metabolism
  • Kidney Diseases/pathology
  • Kidney/pathology
  • Ureteral Obstruction/complications

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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