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
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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