Ptprz Signaling, Tubule-Mediated and Macrophage-Mediated Kidney Injury, and Subsequent CKD
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Le résumé fourni par la source
Key Points Ischemia/reperfusion injury induces Ptprz in mouse kidney tubules and macrophages. Stimulated tubules and macrophages expressing Ptprz promote kidney destruction. Ptprz is similarly expressed in inflamed mouse and human (transplant) kidneys, thus are translational. Background Macrophages and tubular epithelial cell interactions are integral in kidney ischemia-incited interstitial inflammation leading to AKI. Ischemia/reperfusion injury triggers tubular epithelial cells to express IL-34, a macrophage growth factor, that promotes AKI and subsequent CKD. IL-34 engages the cognate receptor, c-FMS, expressed by macrophages, and the recently discovered protein-tyrosine phosphatase ζ (Ptprz). Ptprz binds to multiple ligands other than IL-34 that progressively increase their expression in kidneys after ischemia/reperfusion injury. Methods We tested the hypothesis that signaling through Ptprz promotes macrophage-mediated AKI and subsequent CKD by comparing Ptprz knockout with wild-type mice after ischemia/reperfusion injury. Results Ptprz was expressed by leukocytes and in tubular epithelial cells after ischemia/reperfusion injury in mice. Using Ptprz knockout mice, we determined that during AKI and CKD kidney pathology, loss of kidney function was ameliorated. Ptprz-dependent mechanisms mediated: ( 1 ) tubular epithelial cell expression of chemokines that fostered macrophage and T-cell–rich renal inflammation and ( 2 ) tubule injury and apoptosis, which resulted in the loss of tubules and interstitial fibrosis during CKD. Mechanistically, Ptprz-dependent tubule epithelial cells released mediators that ( 1 ) promoted tubule cytotoxicity and, thereby, shortened tubule survival and ( 2 ) stimulated Ptprz-expressing macrophages to generate mediators that induce kidney destruction. These findings are translational, as after ischemia-reperfusion injury in human kidney transplants, protein-tyrosine phosphasase zeta (PTPRZ) and PTPRZ ligands were upregulated and expressed by the same cell populations as in mice. Moreover, PTPRZ levels in sera were elevated in kidney transplant patients. Conclusions Intrarenal Ptprz-dependent macrophage and tubular epithelial cell–mediated mechanisms promote AKI and subsequent CKD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Ptprz Signaling, Tubule-Mediated and Macrophage-Mediated Kidney Injury, and Subsequent CKD
- Date Crossref
- 11/02/2025
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Johannes Gutenberg University Mainz Department of Nephrology pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center of the Johannes Gutenberg University Mainz pays non établi dans la noticeÉtablissement de santé
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Brigham and Women's Hospital Department of Medicine pays non établi dans la noticeÉtablissement de santé
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Instituto Nacional de Salud Pública CONACYT – Centro de Investigación Sobre Enfermedades Infecciosas pays non établi dans la noticeOrganisme public
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Secretaría de Ciencia pays non établi dans la noticeOrganisme public
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Kanazawa University Department of Nephrology and Rheumatology pays non établi dans la noticeUniversité ou école supérieure
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Research Center for Immunotherapy (FZI) Mainz pays non établi dans la noticeStructure de recherche
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University Medical Center Mainz Institute of Medical Biostatistics pays non établi dans la noticeUniversité ou école supérieure
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Homeostatic Mechanism Research Unit pays non établi dans la noticeStructure de recherche
Department of Nephrology — Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz et Department of Medicine — Brigham and Women's Hospital, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.