The cannabinoid receptor 1 is involved in renal fibrosis during chronic allograft dysfunction: Proof of concept
Autor: | Sophie Vandermeersch, Antoine Durrbach, Lola Lecru, Mélanie Ferreira, Christos Chatziantoniou, Bogdan Hermeziu, Katia Posseme, Hélène François, Myriam Dao, Charlotte Mussini, Sophie Ferlicot |
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Přispěvatelé: | Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Galapagos SASU [Romainville, France], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cannabinoid receptor [SDV]Life Sciences [q-bio] Mice 0302 clinical medicine Receptor Cannabinoid CB1 Rimonabant Fibrosis Cells Cultured Kidney [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology chronic allograft dysfunction Middle Aged renal transplantation Endocannabinoid system renal fibrosis 3. Good health [SDV] Life Sciences [q-bio] medicine.anatomical_structure 030220 oncology & carcinogenesis Molecular Medicine Original Article Female lipids (amino acids peptides and proteins) Immunosuppressive Agents medicine.drug medicine.medical_specialty Tacrolimus 03 medical and health sciences Internal medicine Renal fibrosis medicine Animals Humans Retrospective Studies business.industry Original Articles Cell Biology medicine.disease Kidney Transplantation Mice Inbred C57BL Transplantation cannabinoid receptor 1 030104 developmental biology Endocrinology Chronic Disease Primary Graft Dysfunction business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
Zdroj: | Journal of Cellular and Molecular Medicine Journal of Cellular and Molecular Medicine, Wiley Open Access, 2019, 23 (11), pp.7279-7288. ⟨10.1111/jcmm.14570⟩ |
ISSN: | 1582-1838 1582-4934 |
Popis: | International audience; Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney-transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post-transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus-mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology. |
Databáze: | OpenAIRE |
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