{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:49:44Z","timestamp":1789429784615,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01-DK095867"],"award-info":[{"award-number":["R01-DK095867"]}]},{"name":"NIH","award":["R01-DK0124259"],"award-info":[{"award-number":["R01-DK0124259"]}]},{"name":"NIH","award":["15GRNT25700209"],"award-info":[{"award-number":["15GRNT25700209"]}]},{"name":"NIH","award":["NSFC 82170761"],"award-info":[{"award-number":["NSFC 82170761"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01-DK095867"],"award-info":[{"award-number":["R01-DK095867"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01-DK0124259"],"award-info":[{"award-number":["R01-DK0124259"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["15GRNT25700209"],"award-info":[{"award-number":["15GRNT25700209"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["NSFC 82170761"],"award-info":[{"award-number":["NSFC 82170761"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Foundation of China","award":["R01-DK095867"],"award-info":[{"award-number":["R01-DK095867"]}]},{"name":"National Science Foundation of China","award":["R01-DK0124259"],"award-info":[{"award-number":["R01-DK0124259"]}]},{"name":"National Science Foundation of China","award":["15GRNT25700209"],"award-info":[{"award-number":["15GRNT25700209"]}]},{"name":"National Science Foundation of China","award":["NSFC 82170761"],"award-info":[{"award-number":["NSFC 82170761"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells12020214","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T04:28:17Z","timestamp":1672806497000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Notch Blockade Specifically in Bone Marrow-Derived FSP-1-Positive Cells Ameliorates Renal Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Yongdong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China"},{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China"},{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhang","family":"Huang","sequence":"additional","affiliation":[{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1523-1755.2005.00422.x","article-title":"Macrophages and progressive tubulointerstitial disease","volume":"68","author":"Cockwell","year":"2005","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1046\/j.1523-1755.2001.0590051626.x","article-title":"Role of immunocompetent cells in nonimmune renal diseases","volume":"59","author":"Pons","year":"2001","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"528","DOI":"10.2353\/ajpath.2010.090526","article-title":"S100A4 and metastasis: A small actor playing many roles","volume":"176","author":"Boye","year":"2010","journal-title":"Am. 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